John H. Frenster

Division of Oncology, Department of Medicine,
Stanford University School of Medicine, Stanford, California 94305. 

Summary:
Introduction:
DNase I, Materials and Methods:
Results:
Discussion:
Conclusions:
Acknowledgements:
Support:
References:
Additional References: (Electron Micrographs of Human Bone Marrow and Lymph Nodes):
Links to Related WebSites:

SUMMARY

An electron microscopic technique has been developed to visualize the binding sites of acridine orange to DNA within fixed human leukemic bone marrow cells. This electron microscopic technique provides both higher resolution and increased chemical specificity for discriminating the nuclear binding sites of acridine orange than does the previous fluorescent light microscopy. Acridine orange binds to DNA exclusively within the active extended euchromatin portion of the cell nucleus. This locale of binding is predicted by the molecular model of gene derepression within interphase mammalian chromatin and correlates with the effects of this ligand on RNA synthesis and on the conversion of euchromatin to heterochromatin by this and other nuclear ligands.

INTRODUCTION

Acridine orange is a useful fluorescence microscopy probe for studying the changes in conformation of nuclear chromatin during lymphocyte activation by phytohemagglutinin (19,20), nucleated erythrocyte activation after cell hybridization (6), atypical activation of lymphocytes in infectious mononucleosis (5), cell inactivation during spermatogenesis (17, 25), and cell inactivation during culture at high cell densities (4, 30).

When used in such microspectrofluorimetric analyses of single fixed cells, acridine orange probes can physically distinguish single-stranded nucleic acid binding sites from double-stranded sites (23), but cannot chemically distinguish DNA binding sites from RNA sites (23). With the increasing evidence for the intracellular presence of double-stranded RNA duplexes (13, 18) and single-stranded DNA loops (13), this low chemical specificity has become critical in the further use of the probe. In addition, the low resolution of separate binding sites possible with fluorescent light microscopy suggested the need for the development of a high resolution electron microscopic technique for detecting acridine orange binding sites specific for DNA. The development of such an ultrastuctural probe method has permitted high resolution studies of intranuclear binding sites within human leukemic bone marrow cells (11).

MATERIALS AND METHODS

Bone marrow samples were aspirated from untreated leukemic patients undergoing diagnostic marrow examination . Informed consent was obtained from the patient in all cases. A total of 2.0 ml was aspirated in each case, of which a 1.0 ml aliquot was used for the acridine orange study. Particulate marrow spicules were separated from aspirated blood by adhesion to an inclined slide and were allowed to react at 4^o C. and pH 7.2 for 2 hr with 10^-3 M acridine orange (K and K Laboratories, Plainview, N.Y., twice recrystallized ) in Medium 199 (Grand Island Biological Co., Grand Island, N.Y.) after fixation at 4^o C. with 5% glutaraldehyde in Medium 199 at pH 6.5 for 2 hr. The stained spicules were then washed 3 times in Medium 199 and incubated at 37^o C. for 30 min in low-calcium spinner-type Eagle's minimal essential medium (Grand Island Biological Co.) at pH 7.4 and 0.8 mM Mg⁺⁺ containing containing either DNase I (Worthington Biochemical Corp., Freehold, N.J.; electrophoretically separated from any contaminating RNase activity), RNase (Worthington, electrophoretically pure), trypsin (Worthington, crystallized 3 times) at a concentration of 1.0 mg/ml, or no enzyme in control aliquots. The incubated spicules were then prepared for electron microscopy (16) by being postfixed in 1% OsO₄, dehydrated in ethanol, embedded in Epon, sectioned 0.1 um thick, stained with 5% uranyl acetate, and examined at 80 kV under high resolution in a Siemens 1A electron microscope. Parallel microspectrofluorimetric examinations (24) were performed on alternate 1.0 um thick sections with a Zeiss MPM microspectrofluorimeter. Replicate control samples from a single aspiration either omitted the acridine orange or substituted 10^-3 carbodiimide (1, 26) (Aldrich Chemical Co., Inc. Milwaukee, Wis., twice recrystallized) for the acridine orange.

RESULTS

Human bone marrow cells that are caused to react with 10^-3 M acridine orange after glutaraldehyde fixation and are then digested with DNase display a characteristic electron-dense reaction product, approximately 0.1 um in diameter, which is clearly visible by high-resolution electron microscopy (Figs. 1 to 4).
Fig. 1. Electron micrograph of a marrow spicule aspirated from an untreated patient with chronic myelogenous leukemia and caused to react with acridine orange followed by DNase digestion (see text). Electron-dense reaction products, 0.1 um in diameter, are confined to the euchromatin portion of the cell nucleus of each cell in the spicule. X 2,500.
Fig. 2. Electron micrograph of a nucleated erythrocyte from the same marrow spicule as in Fig. 1 prepared in the same manner. Electron-dense reaction products, 0.1 um in diameter, are confined to the euchromatin portion of the cell nucleus. X 10,000.
Fig. 3. Electron micrograph of a myelocyte from another untreated patient with chronic myelogenous leukemia prepared in the same manner as those in Figs. 1 and 2. Electron-dense reaction products, 0.1 um in diameter, are confined to the euchromatin portion of the cell nucleus. X 7,500.
Fig. 4. Electron micrograph of a nucleated erythrocyte fron a 3rd untreated patient with chronic myelogenous leukemia prepared in the same manner as those shown in Figs. 1 to 3. Electron-dense reaction products, 0.1 um in diameter, are confined to euchromatin portion of the cell nucleus. X 10,000.

The reaction product is visible in each of the cells of a particular marrow spicule (Fig. 1) and is confined to the nucleus of each cell, never being found within the cytoplasm of such cells (Figs. 2 to 4). Within each cell nucleus, the reaction product is confined to the extended euchromatin portion of the cell nucleus (Figs. 2 to 4), never being found within the condensed heterochromatin portion or within the nucleolar portion of the cell nucleus. The reaction product is found within all types of cells of the marrow spicule, including nucleated erythrocytes, myelocytes, megakaryocytes, reticulum cells, histiocytes, and lymphocytes (Figs. 1 to 4).

If acridine orange is omitted from the preparation sequence (Table 1) or if carbodiimide, another ligand to DNA (1, 26), is substituted for acridine orange, the characteristic reaction product is not observed (Table 1).
 

Table 1. Reaction product formation after nuclear ligand binding and enzymatic digestion. The concentration of the nuclear ligand in the reaction solution is 1.0 mM. The concentration of the enzyme in the digestion solution is 1.0 mg/ml.

Nuclear Ligand	Enzyme
	None	DNase	RNase	Trypsin
None	0*	0	0	0
Acridine orange	0	+	0	0
Carbodiimide	0	0	0	0
*0, no reaction product visible; +, prominent reaction product visible.

Similarly, if DNase is omitted from the preparation sequence, or if RNase or trypsin are substituted for DNase, the characteristic reaction product is not observed (Table 1). These control data indicate that both reaction with acridine orange and digestion with DNase are necessary for visualization of the reaction product (Table 1), and strongly suggest that the reaction product is formed as a result of the interaction of acridine orange with DNA binding sites within the euchromatin portion of the cell nucleus. In view of previous studies, which indicate resistance to DNase digestion after glutaraldehyde fixation (3), additional studies are currently in progress to define the molecular composition of the reaction with acridine orange binding and DNase digestion in isolated DNA and isolated euchromatin (16) systems.

DISCUSSION

Acridine orange binds to isolated DNA via each of 2 physical binding modes: (a) a stacking interaction resulting from the intercalation of acridine orange molecules between adjacent base pairs within the interior of the DNA helix at low ratios of ligand to nucleic acid (21) and: (b) an electrostatic interaction between the basic groups of the acridine orange molecule and the acidic phosphate groups on the exterior of the DNA helix at high ratios of ligand to nucleic acid (22). The prior presence of polycationic proteins, such as histones, on the DNA helix effectively decreases the reactivity of such DNA to acridine orange, both by stabilizing the DNA helix against the strand separation (10) necessary to allow intercalation of acridine orange (21) and by neutralizing the phosphate groups on the exterior of the DNA helix capable of reacting with acridine orange (22). As a consequence of such inhibition of acridine orange binding to DNA by histones, acridine orange microscopic fluorescent probes have been used to distinguish chromatin states in which histones are tightly bound to underlying DNA helices from those in which histones are loosely bound to DNA (24).

The current molecular model of gene derepression within mammalian chromatin (10) indicates that histones within active extended euchromatin are less tightly bound to underlying DNA than are the histones within repressed condensed heterochromatin (9). On this basis, it might be expected that a molecular probe such as acridine orange, which requires access to DNA in order to bind to DNA (24), would preferentially bind to DNA within euchromatin rather than to DNA within heterochromatin (13), although the largest part of nuclear DNA is contained within heterochromatin (13, 16). This expectation is strikingly confirmed in the present study, in which the vast majority of the reaction product of acridine orange binding to DNA is found in the euchromatin portion of the cell nucleus, with little or none found in the heterochromatin portion (Figs. 2 to 4).

This distribution of acridine orange binding to DNA is similar to the finding that actinomycin D, another ligand with a high affinity for DNA, similarly binds preferentially to the euchromatin rather than the heterochromatin portion of the cell nucleus (2).
 

Table 2. Correlation of nuclear binding site with ligand effect on RNA synthesis. Localization of nuclear ligand determined by electron microscopy and appropriate enzymatic digestion (see text).

Nuclear Ligand	Nuclear Binding Site	Ligand Effect on RNA Synthesis
Acridine orange	DNA within euchromatin (this study)	Decreases (13)
Actinomycin D	DNA within euchromatin (2)	Decreases (13)
Phytohemagglutinin	Histones within heterochromatin (27)	Increases (7)
Mercuric chloride	Histones within heterochromatin (14)	Increases (23)

In fact (Table 2), both of these ligands to DNA, while localized preferentially to the euchromatin portion of the nucleus, are also similar in that both are inhibitors of RNA synthesis (13, 14) and both induce the conversion of euchromatin to heterochromatin following their binding to the DNA of euchromatin (8, 28). By contrast, both phytohemagglutinin (7) and mercuric chloride (23) are nuclear ligands that increase RNA synthesis (Table 2) and induce the conversion of heterochromatin to euchromatin (23, 29). Previous electron microscopic studies have shown that both phytohemagglutinin (12, 27) and mercuric chloride (12, 14) are localized within the heterochromatin portion of the cell nucleus of cells responding to these ligands. The binding of each of these 2 ligands is sensitive to trypsin digestion (14, 27), suggesting that the binding site of both phytohemagglutinin and mercuric chloride may be the histones of condensed heterochromatin (14, 27). Such histones within condensed heterochromatin are more exposed to potential ligands than are the histones within extended euchromatin, since the latter are displaced from underlying DNA helices by nuclear polyanions such as derepressor RNA (10), phosphoproteins, and acidic and hydrophobic nonhistone proteins (9).

These data indicate (Table 2) that DNA ligands (acridine orange, actinomycin D) localize preferentially to active extended euchromatin, where they effect an inhibition of RNA synthesis and a conversion of euchromatin to heterochromatin, while histone ligands (phytohemagglutinin, mercuric chloride) localize preferentially to repressed condensed heterochromatin, where they effect an activation of RNA synthesis and a conversion of heterochromatin to euchromatin (12, 14).

There thus appear to be a variety of nuclear ligands with specific binding sites that can be visualized by high-resolution electron microscopy, and with actions effecting cell activation or inactivation that are profound following such binding (14). Such ultrastructural probes of chromatin conformation states are currently being utilized for analyses of neoplastic and of differentiating cells (15).

ACKNOWLEDGEMENTS

I thank the study patients for their kindness and generosity, the referring physicians for their cooperation, and Marie A. Shatos and Cheryl C. Hayden for their technical assistance in embedding, sectioning, and staining the marrow samples.

SUPPORT

This investigation was supported in part by Research Grant CA-10174 from the National Cancer Institute, and by a Research Scholar Award from the Leukemia Society.

REFERENCES

1. Augusti-Tocco G, and Brown GL, "Reactions of N-Cyclohexyl, N'-B (4-Methylmorpholinium) Ethyl Carbodiimide Iodide with Nucleic Acids and Polynucleotides", Nature 206, 683-685 (1965).

2. Berlowitz L, Pallotta D, and Sibley CH, "Chromatin and Histones: Binding of Tritiated Actinomycin D to Heterochromatin in in Mealy Bugs", Science 164, 1527-1529 (1969).

3. Bernard W, and Granboulan N, "The Fine Structure of the Cancer Cell Nucleus", Exptl. Cell Res. Suppl. 9, 19-53 (1963).

4. Bolund L, Darzynkiewicz Z, and Ringertz NR, "Cell Concentration and the Staining Properties of Nuclear Deoxyribonucleoprotein", Exptl. Cell Res. 62, 76-89 (1970).

5. Bolund L, Gahrton G, Killander D, Rigler R, and Wahren B, "Structural Changes in Deoxyribonucleoprotein Complex of Leukocytes from Patients with Infectious Mononucleosis", Blood 35, 322-332 (1970).

6. Bolund L, Ringertz NR, and Harris H, "Changes in the Cytochemical Properties of Erythrocyte Nuclei Reactivated by Cell Fusion", J. Cell Sci. 4, 71-87 (1969).

7. Cooper HL, "Ribonucleic Acid Metabolism in Lymphocytes Stimulated by Phytohemagglutinin", J. Biol. Chem. 243, 34-43 (1968).

8. DeMan JCH, and Noorduyn NJA, "Light and Electron Microscopic Radioautography of Hepatic Cell Nucleoli in Mice Treated with Actinomycin D", J. Cell Biol. 33, 489-496 (1967).

9. Frenster JH, "Nuclear Polyanions as De-repressors of Synthesis of Ribonucleic Acid ", Nature 206, 680-683 (1965).

10. Frenster JH, "A Model of Specific De-repression Within Interphase Chromatin", Nature 206, 1269-1270 (1965).

11. Frenster JH, "Electron Microscope Localization of Acridine Orange Binding within Nuclei of Human Leukemic Bone Marrow Cells ", J. Cell Biol. 43, 39a (1969).

12. Frenster JH, "Electron Microscopic Localization of Nuclear Binding within Human Leukocytes", Blood 34, 847 (1969).

13. Frenster JH, "Biochemistry and Molecular Biophysics of Heterochromatin and Euchromatin", in: Lima-de-Faria A, (ed.) "Handbook of Molecular Cytology", pp. 251-276, Amsterdam: North-Holland Publishing Co., 1969.

14. Frenster JH, "Ultrastuctural Binding Sites Correlate with Effects of Nuclear Ligands on RNA Synthesis within Human Leukocytes", in: Zbarsky IB, (ed.) "Structure and Functions of the Cell Nucleus", pp. 129-147 , Moscow: Institute of Developmental Biology of the Academy of Sciences, 1970.

15. Frenster JH, "Gene De-repression within Human Neoplasms and within Immunotherapeutic Human Lymphocytes", J. Cell Biol. 47, 65a-66a (1970).

16. Frenster JH, Allfrey VG, and Mirsky AE, "Repressed and Active Chromatin Isolated from Interphase Lymphocytes", Proc. Natl. Acad. Sci. U.S. 50, 1026-1032 (1963).

17. Gledhill BL, Gledhill MP, Rigler R, and Ringertz NR, "Changes in Deoxyribonucleoprotein during Spermiogenesis in the Bull", Exptl. Cell Res. 41, 652-665 (1966).

18. Harel L, and Montagnier L, "Homology of Double Stranded RNA from Rat Liver Cells with the Cellular Genome", Nature 229, 106-108 (1971).

19. Keshgegian AA, Meisner LF, and Frenster JH, "Thymidine Reversal of Ribothymidine Inhibition of Lymphocyte Mitosis", in McIntyre OR, (ed.) "Proceedings of the Fourth Annual Leukocyte Culture Conference", pp. 361-366, New York: Appleton-Century-Crofts, Inc. 1971.

20. Killander D, and Rigler R, "Activation of Deoxyribonucleoprotein in Human Leukocytes Stimulated by Phytohemagglutinin", Exptl. Cell Res. 54, 163-170 (1969).

21. Lerman LS, "The Structure of the DNA-Acridine Complex", Proc. Natl. Acad. Sci. U.S. 49, 94-102 (1963).

22. Mason SF, and McCaffery AJ, "Optical Rotatory Power of DNA and of Its Complex with Acridine Orange under Streaming Conditions", Nature 204, 468-470 (1964).

23. Pauly JL, Caron GA, and Suskind RR, "Blast Transformation of Lymphocytes from Guinea Pigs, Rats, and Rabbits Induced by Mercuric Chloride in Vitro", J. Cell Biol. 40, 847-850 (1969).

24. Rigler R, "Acridine Orange in Nucleic Acid Analysis", Ann. N.Y. Acad. Sci. 157, 211-224 (1969).

25. Ringertz NR, Gledhill BL, and Darzynkiewicz Z, "Changes in Deoxyribonucleoprotein during Spermiogenesis in the Bull", Exptl. Cell Res. 62, 204-218 (1970).

26. Salganik RI, Dashkevich VS, and Dymshits GM, "Studies of Replicating DNA of Regenerating Rat Liver Using Chemical Modifications with Water-Soluble Carbodiimide", Biochim. Biophys. Acta 149, 603-606 (1967).

27. Stanley DA, Frenster JH, and Rigas DA, "Localization of ³H-Phytohemagglutinin within Human Lymphocytes and Monocytes", In: McIntyre OR (ed.), "Proceedings of the Fourth Annual Leukocyte Culture Conference", pp. 1-11, New York: Appleton-Century-Crofts, Inc. 1971.

28. Stevens BJ, "The Effects of Actinomycin D on Nucleolar and Nuclear Fine Structure in Salivary Gland Cell of Chironomus thummi", J. Ultrastruct. Res. 11, 329-354 (1964).

29. Tokuyasu K, Malden SC, and Zeldis LJ, "Fine Structural Alterations of Interphase Nuclei of Lymphocytes Stimulated to Growth Activity in Vitro", J. Cell Biol. 39, 630-660 (1968).

30. Zetterberg A, and Auer G, "Proliferative Activity and Cytochemical Properties of Nuclear Chromatin Related to Local Density of Epithelial Cells", Exptl. Cell Res. 62, 262-270 (1970). 

1. Frenster JH, "Ultrastructural Effects of Mercuric Chloride on Nuclear Heterochromatin within Human Lymphocytes", J. Cell Biol. vol. 43, pp. 39a-40a (1969).

2. Frenster JH, "Correlation between the Ultrastructural Binding Site of Nuclear Ligands and the Effect of the Ligand on RNA Synthesis in Human Leukocytes", J. Cell Biol. vol. 47, p. 65a (1970).

3. Ahearn MJ, and Trujillo JM, "Cytogenetic and Ultrastructural Evidence of Altered DNA Metabolism in Leukemic Cells", Proc. Am. Assoc. Cancer Research 13: 108 (March, 1972).

4. Frenster JH, Nakatsu SL, and Masek MA, "Ultrastuctural Probes of DNA Templates within Human Bone Marrow and Lymph Node Cells", in "Advances in Cell and Molecular Biology", (DuPraw EJ, ed.).
vol. 3, pp. 1-19 (1974), New York: Academic Press.
Text, Tables, and References: pp. 1-19.
Electron Micrographs during Cell Differentiation within Normal Human Bone Marrow: pp. 4-8.
Electron Micrographs during Cell Activation within Human Hodgkin's Disease Lymph Nodes: pp. 8-17.

5. Kumakiri M, and Hashimoto K, "Acridine Orange-DNA Complex in Actinic Keratosis", J. Natl. Cancer Inst. 59: 839-844 (September, 1977).

Related References to this Paper in PubMed:

1:  Frenster JH.
 Electron microscopic localization of acridine orange binding to DNA within
human leukemic bone marrow cells.
Cancer Res. 1971 Aug;31(8):1128-33. No abstract available.
PMID: 5285975 [PubMed - indexed for MEDLINE]

2:  Moriki T, Hiroi M, Yamane T, Hara H.
 Effects of actinomycin D on localization of acridine orange chromatin
interaction complex in rat astrocytoma C6 cells.
Acta Pathol Jpn. 1986 Mar;36(3):389-98.
PMID: 3716793 [PubMed - indexed for MEDLINE]

3:  Vladimirskaya EB, Simonov EE, Balakhovskii IS, Ivanova IE.
 Proliferative activity of leukemic cells in acute leukemia.
Fed Proc Transl Suppl. 1966 Jul-Aug;25(4):633-6. No abstract available.
PMID: 5223505 [PubMed - indexed for MEDLINE]

4:  Moriki T, Kimura S, Yamane T, Hara H.
 Electron microscopic localization of acridine orange chromatin interaction
products in cells transformed by herpes simplex virus type 2.
Acta Pathol Jpn. 1988 Jun;38(6):693-704.
PMID: 2851256 [PubMed - indexed for MEDLINE]

5:  Micu D, Mihailescu E, Raiciulescu N, Cheta D, Olinescu V.
 Asynchronisms between DNA and RNA synthesis in leukemic cells.
Rev Roum Med Intern. 1974;11(2):229-33. No abstract available.
PMID: 4522961 [PubMed - indexed for MEDLINE]

6:  Moriki T, Hiroi M, Hara H, Taniguchi T, Shizuta Y, Yamane T.
 Effects of methylnitrosourea on visualization of acridine orange binding to DNA
in mouse lymphoma L-1210 cells.
Pathol Res Pract. 1986 May;181(2):206-12.
PMID: 3090524 [PubMed - indexed for MEDLINE]

7:  Emura I, Naito M, Kakihara T, Wakabayashi M, Hayashi N, Chou T.
 Identification of drug-resistant myeloid leukemic cells by measurement of DNA
content, nuclear area, and detection of P-glycoprotein.
Cancer. 1996 Mar 1;77(5):878-87.
PMID: 8608478 [PubMed - indexed for MEDLINE]

8:  Bendall LJ, Kortlepel K, Gottlieb DJ.
 Bone marrow fibroblast exposure to the inflammatory cytokines tumor necrosis
factor-alpha and interferon-gamma increases adhesion of acute myeloid leukemia
cells and alters the adhesive mechanism.
Exp Hematol. 1997 Feb;25(2):132-9.
PMID: 9015213 [PubMed - indexed for MEDLINE]

9:  Pileri A, Masera P, Garbarino G, Hulin N.
 Myeloid cell actinomycin binding in human myeloid leukaemia.
Acta Haematol. 1974;51(1):1-8. No abstract available.
PMID: 4217070 [PubMed - indexed for MEDLINE]

10:  Barlogie B, Latreille J, Freireich EJ, Fu CT, Mellard D, Meistrich M,
Andreeff M.
 Characterization of hematologic malignancies by flow cytometry.
Blood Cells. 1980;6(4):719-44.
PMID: 7008871 [PubMed - indexed for MEDLINE]

11:  Bendall LJ, Daniel A, Kortlepel K, Gottlieb DJ.
 Bone marrow adherent layers inhibit apoptosis of acute myeloid leukemia cells.
Exp Hematol. 1994 Dec;22(13):1252-60.
PMID: 7957711 [PubMed - indexed for MEDLINE]

12:  Nakatsu SL, Masek MA, Landrum S, Frenster JH.
 Activity of DNA templates during cell division and cell differentiation.
Nature. 1974 Mar 22;248(446):334-5. No abstract available.
PMID: 4132100 [PubMed - indexed for MEDLINE]

13:  Trubowitz S, Broers A, Pease RF.
 Surface ultrastructure of the human marrow--a brief note.
Blood. 1970 Jan;35(1):112-5. No abstract available.
PMID: 5263118 [PubMed - indexed for MEDLINE]

14:  Choksey AF, Sirsat SM, Jussawalla DJ.
 Ultrastructural localization of acridine orange binding to DNA of human breast
cancer cells.
Indian J Exp Biol. 1977 Aug;15(8):601-5. No abstract available.
PMID: 203525 [PubMed - indexed for MEDLINE]

15:  Dmochowski L, Allen PT, Newton WA Jr, Georgiades J, Maruyama K, East JL,
Bowen JM.
 Studies on transforming activities from human solid tumor cells following
co-cultivation with human leukemic bone marrow cells.
Johns Hopkins Med J Suppl. 1973;2:157-79. No abstract available.
PMID: 4137954 [PubMed - indexed for MEDLINE]

16:  Gorius JB, Houssay D.
 Auer bodies in acute promyelocytic leukemia. Demonstration of their fine
structure and peroxidase localization.
Lab Invest. 1973 Feb;28(2):135-41. No abstract available.
PMID: 4347100 [PubMed - indexed for MEDLINE]

17:  Dybkaer K, Olesen G, Pedersen FS, Kristensen JS.
 Stromal-mediated down-regulation of CD13 in bone marrow cells originating from
acute myeloid leukemia patients.
Eur J Haematol. 2001 Mar;66(3):168-77.
PMID: 11350485 [PubMed - indexed for MEDLINE]

18:  Frenster JH.
 Ultrastructural probes of chromatin within living human lymphocytes.
Nat New Biol. 1972 Apr 12;236(67):175-6. No abstract available.
PMID: 4113338 [PubMed - indexed for MEDLINE]

19:  Whang-Peng J, Leventhal BG, Adamson JW, Perry S.
 The effect of daunomycin on human cells in vivo and in vitro.
Cancer. 1969 Jan;23(1):113-21. No abstract available.
PMID: 5249421 [PubMed - indexed for MEDLINE]

20:  Hara H, Moriki T, Hiroi M, Yamane T.
 Electron microscopic localization of acridine orange binding to DNA within rat
astrocytoma C6 cells.
Acta Pathol Jpn. 1984 Sep;34(5):1049-57.
PMID: 6507087 [PubMed - indexed for MEDLINE]

21:  Bradstock KF, Gottlieb DJ.
 Interaction of acute leukemia cells with the bone marrow microenvironment:
implications for control of minimal residual disease.
Leuk Lymphoma. 1995 Jun;18(1-2):1-16. Review.
PMID: 8580810 [PubMed - indexed for MEDLINE]

22:  Ishiguro A, Spirin KS, Shiohara M, Tobler A, Gombart AF, Israel MA, Norton
JD, Koeffler HP.
 Id2 expression increases with differentiation of human myeloid cells.
Blood. 1996 Jun 15;87(12):5225-31.
PMID: 8652837 [PubMed - indexed for MEDLINE]

23:  Weber-Nordt RM, Egen C, Wehinger J, Ludwig W, Gouilleux-Gruart V,
Mertelsmann R, Finke J.
 Constitutive activation of STAT proteins in primary lymphoid and myeloid
leukemia cells and in Epstein-Barr virus (EBV)-related lymphoma cell lines.
Blood. 1996 Aug 1;88(3):809-16.
PMID: 8704235 [PubMed - indexed for MEDLINE]

24:  Smith WC, Kaneshiro MM, Goldstein BD, Parker JW, Lukes RJ.
 Gaucher cells in chronic granulocytic leukaemia.
Lancet. 1968 Oct 5;2(7571):780-1. No abstract available.
PMID: 4175579 [PubMed - indexed for MEDLINE]

25:  Andreeff M, Darzynkiewicz Z, Sharpless TK, Clarkson BD, Melamed MR.
 Discrimination of human leukemia subtypes by flow cytometric analysis of
cellular DNA and RNA.
Blood. 1980 Feb;55(2):282-93.
PMID: 6928106 [PubMed - indexed for MEDLINE]

26:  Stopka T, Zakova D, Fuchs O, Kubrova O, Blafkova J, Jelinek J, Necas E,
Zivny J.
 Chromatin remodeling gene SMARCA5 is dysregulated in primitive hematopoietic
cells of acute leukemia.
Leukemia. 2000 Jul;14(7):1247-52.
PMID: 10914549 [PubMed - indexed for MEDLINE]

27:  Brown CH 3rd, Carbone PP.
 In vitro growth of normal and leukemic human bone marrow.
J Natl Cancer Inst. 1971 May;46(5):989-1000. No abstract available.
PMID: 5290566 [PubMed - indexed for MEDLINE]

28:  Erickson PF, Dessev G, Lasher RS, Philips G, Robinson M, Drabkin HA.
 ETO and AML1 phosphoproteins are expressed in CD34+ hematopoietic progenitors:
implications for t(8;21) leukemogenesis and monitoring residual disease.
Blood. 1996 Sep 1;88(5):1813-23.
PMID: 8781439 [PubMed - indexed for MEDLINE]

29:  Weber MC, Tykocinski ML.
 Bone marrow stromal cell blockade of human leukemic cell differentiation.
Blood. 1994 Apr 15;83(8):2221-9.
PMID: 7512844 [PubMed - indexed for MEDLINE]

30:  Bullock G, Tang C, Tourkina E, Ibrado AM, Lutzky J, Huang Y, Mahoney ME,
Bhalla K.
 Effect of combined treatment with interleukin-3 and interleukin-6 on
4-hydroperoxycyclo-phosphamide-induced programmed cell death or apoptosis in
human myeloid leukemia cells.
Exp Hematol. 1993 Dec;21(13):1640-7.
PMID: 8243566 [PubMed - indexed for MEDLINE]

31:  Yamada O, Oshimi K, Motoji T, Mizoguchi H.
 Telomeric DNA in normal and leukemic blood cells.
J Clin Invest. 1995 Mar;95(3):1117-23.
PMID: 7883960 [PubMed - indexed for MEDLINE]

32:  Namikawa R, Ueda R, Kyoizumi S.
 Growth of human myeloid leukemias in the human marrow environment of SCID-hu
mice.
Blood. 1993 Oct 15;82(8):2526-36.
PMID: 8104540 [PubMed - indexed for MEDLINE]

33:  Chervenick PA, Ellis LD, Pan SF, Lawson AL.
 Human leukemic cells: in vitro growth of colonies containing the Philadelphia
(Ph) chromosome.
Science. 1971 Dec 10;174(14):1134-6. No abstract available.
PMID: 5289582 [PubMed - indexed for MEDLINE]

34:  Recher I, Chan H, Sykes JA.
 Comparative study of microspherules and acridine orange reaction products.
J Ultrastruct Res. 1973 Sep;44(5):347-54. No abstract available.
PMID: 4128206 [PubMed - indexed for MEDLINE]

35:  Ito S.
 [Electron microscopic study of the leukemic cells in the bone marrow]
Nippon Ketsueki Gakkai Zasshi. 1966 Feb;29(1):22-41. Japanese. No abstract
available.
PMID: 6006290 [PubMed - indexed for MEDLINE]

36:  Reuter C, Schleyer E, Rolf C, Wormann B, Buchner T, Hiddemann W.
 Differential effect of GM-CSF pretreatment on intracellular Ara-C metabolism in
normal bone marrow mononuclear cells vs acute myeloid leukemia (AML) blasts.
Leukemia. 1997 Apr;11(4):561-71.
PMID: 9096697 [PubMed - indexed for MEDLINE]

37:  Lee RE, Ellis LD.
 The storage cells of chronic myelogenous leukemia.
Lab Invest. 1971 Apr;24(4):261-4. No abstract available.
PMID: 4933762 [PubMed - indexed for MEDLINE]

38:  Hathaway WE, Newby LA, Githens JH.
 The acridine orange viability test applied to bone marrow cells. II.
Correlation with an in vivo irradiated mouse assay.
Cryobiology. 1965 Nov-Dec;2(3):143-6. No abstract available.
PMID: 4159431 [PubMed - indexed for MEDLINE]

39:  Lenskaia RV, Shishkanova ZG, Cherntsova TA, Terent'eva EI.
 [A cytologic study of the elements of hematopoiesis during the blastic crises
of chronic myeloleukemia]
Lab Delo. 1969;10:619-22. Russian. No abstract available.
PMID: 4193061 [PubMed - indexed for MEDLINE]

40:  Chervenick PA, Lawson AL, Ellis LD, Pan SF, McDonald RH Jr.
 In vitro growth of leukemic cells containing the Philadelphia (Ph) chromosome.
J Lab Clin Med. 1971 Nov;78(5):838-9. No abstract available.
PMID: 5288728 [PubMed - indexed for MEDLINE]

41:  SCHNEIBERG K.
 [Studies on nuclei of interphase of bone marrow cells in normal conditions and
in acute chronic myeloid leukemia.]
Patol Pol. 1955 Jan-Mar;6(1):19-28. English, Polish. No abstract available.
PMID: 13245271 [PubMed - indexed for MEDLINE]

42:  Pollack A.
 Electronmicroscopy of leukaemic myeloblasts with numerous lipid-containing
vacuoles.
Scand J Haematol. 1972;9(5):437-41. No abstract available.
PMID: 4116374 [PubMed - indexed for MEDLINE]

43:  Austin GE, Lam L, Zaki SR, Chan WC, Hodge T, Hou J, Swan D, Zhang W, Racine
M, Whitsett C, et al.
 Sequence comparison of putative regulatory DNA of the 5' flanking region of the
myeloperoxidase gene in normal and leukemic bone marrow cells.
Leukemia. 1993 Sep;7(9):1445-50.
PMID: 8396697 [PubMed - indexed for MEDLINE]

44:  Darzynkiewicz Z, Evenson D, Kapuscinski J, Melamed MR.
 Denaturation of RNA and DNA in situ induced by acridine orange.
Exp Cell Res. 1983 Oct;148(1):31-46.
PMID: 6195003 [PubMed - indexed for MEDLINE]

45:  Byrne P, Tew K, Jemionek J, MacVittie T, Erickson L, Schein P.
 Cellular and molecular mechanisms of the bone marrow sparing effects of the
glucose chloroethylnitrosourea chlorozotocin.
Blood. 1984 Apr;63(4):759-67.
PMID: 6322885 [PubMed - indexed for MEDLINE]

46:  Gavosto F, Pileri A, Pegoraro L.
 Proliferation kinetics of acute leukemia cells in relation to the chemotherapy.
Acta Genet Med Gemellol (Roma). 1968 Jan;17(1):30-9. No abstract available.
PMID: 5241851 [PubMed - indexed for MEDLINE]

47:  Takemori N, Hirai K, Onodera R, Uenishi H, Saito N, Takasugi Y, Namiki M,
Muraoka S.
 Disseminated intravascular coagulation in a patient with acute myeloid
leukemia. Ultrastructural evidence of hypercoagulation in bone marrow.
Am J Clin Pathol. 1993 Jun;99(6):695-701.
PMID: 8322704 [PubMed - indexed for MEDLINE]

48:  Zhang JG, Lin F, Chase A, Goldman JM, Cross NC.
 Comparison of genomic DNA and cDNA for detection of residual disease after
treatment of chronic myeloid leukemia with allogeneic bone marrow
transplantation.
Blood. 1996 Mar 15;87(6):2588-93.
PMID: 8630427 [PubMed - indexed for MEDLINE]

49:  Brinkmann W, Dormer P.
 [In vitro procedure for the determination of DNA synthesis duration in
individual cells. Biochemical prerequisites and results]
Histochemie. 1972;30(4):335-43. German. No abstract available.
PMID: 4263196 [PubMed - indexed for MEDLINE]

50:  Ekberg J, Landberg G, Holm C, Richter J, Wolgemuth DJ, Persson JL.
 Regulation of the cyclin A1 protein is associated with its differential
subcellular localization in hematopoietic and leukemic cells.
Oncogene. 2004 Dec 2;23(56):9082-9.
PMID: 15489899 [PubMed - indexed for MEDLINE]

51:  Preisler HD, Raza A, Gopal V, Banavali SD, Bokhari J, Lampkin B.
 The study of acute leukemia cells by means of acridine orange staining and flow
cytometry.
Leuk Lymphoma. 1994 Mar;13(1-2):61-73.
PMID: 7517746 [PubMed - indexed for MEDLINE]

52:  Ruzicka F, Pawlowsky J, Erber A.
 [Spontaneous radial segmentation of the nuclei of myeloblasts in a case of
chronic granulocytic leukemia during blastic crisis. an electromicroscopical
study (author's transl)]
Osterr Z Onkol. 1975;2(6):157-66. German.
PMID: 1064833 [PubMed - indexed for MEDLINE]

53:  Dobrucki J, Darzynkiewicz Z.
 Chromatin condensation and sensitivity of DNA in situ to denaturation during
cell cycle and apoptosis--a confocal microscopy study.
Micron. 2001 Oct;32(7):645-52.
PMID: 11334733 [PubMed - indexed for MEDLINE]

54:  Shimizu T, Tsuruoka N.
 [Cell differentiation and variation in chloroma]
Nippon Ketsueki Gakkai Zasshi. 1971 Mar;34(1):Suppl:21-8. Japanese. No abstract
available.
PMID: 5292462 [PubMed - indexed for MEDLINE]

55:  JIPA G, MICU D.
 [STUDY OF THE BONE MARROW AND BLOOD CELLS IN LEUCOSES WITH THE AID OF THE
FLUORESCENT MICROSCOPE.]
Stud Cercet Med Interna. 1963;38:497-502. Romanian. No abstract available.
PMID: 14059800 [PubMed - indexed for MEDLINE]

56:  Wall CD, Conley PB, Armendariz-Borunda J, Sudarshan C, Wagner JE, Raghow R,
Jennings LK.
 Expression of alpha IIb beta 3 integrin (GPIIb-IIIa) in myeloid cell lines and
normal CD34+/CD33+ bone marrow cells.
Blood Cells Mol Dis. 1997 Dec;23(3):361-76.
PMID: 9398537 [PubMed - indexed for MEDLINE]

57:  Lee C, Lin Y, Huang M, Lin C, Liu C, Chow J, Liu HE.
 Increased cellular glutathione and protection by bone marrow stromal cells
account for the resistance of non-acute promylocytic leukemia acute myeloid
leukemia cells to arsenic trioxide in vivo.
Leuk Lymphoma. 2006 Mar;47(3):521-9.
PMID: 16396776 [PubMed - indexed for MEDLINE]

58:  Polli N, Zola H, Catovsky D.
 Characterization by ultrastructural cytochemistry of normal and leukemic
myeloid cells reacting with monoclonal antibodies.
Am J Clin Pathol. 1984 Oct;82(4):389-95.
PMID: 6591795 [PubMed - indexed for MEDLINE]

59:  Ries C, Loher F, Zang C, Ismair MG, Petrides PE.
 Matrix metalloproteinase production by bone marrow mononuclear cells from
normal individuals and patients with acute and chronic myeloid leukemia or
myelodysplastic syndromes.
Clin Cancer Res. 1999 May;5(5):1115-24.
PMID: 10353746 [PubMed - indexed for MEDLINE]

60:  Soboloff J, Zhang Y, Minden M, Berger SA.
 Sensitivity of myeloid leukemia cells to calcium influx blockade: application
to bone marrow purging.
Exp Hematol. 2002 Oct;30(10):1219-26.
PMID: 12384154 [PubMed - indexed for MEDLINE]

61:  Shimizu K, Ichikawa H, Tojo A, Kaneko Y, Maseki N, Hayashi Y, Ohira M,
Asano S, Ohki M.
 An ets-related gene, ERG, is rearranged in human myeloid leukemia with t(16;21)
chromosomal translocation.
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10280-4.
PMID: 8234289 [PubMed - indexed for MEDLINE]

62:  Shardakov VI, Minakov VN, Fedorovskaia NV.
 [Proliferative activity of leukemic cells taking into account the aggressive
development of chronic myeloleukemia]
Gematol Transfuziol. 1983 Feb;28(2):13-5. Russian. No abstract available.
PMID: 6573287 [PubMed - indexed for MEDLINE]

63:  Holton CP, Johnson WW.
 Chronic myelocytic leukemia in infant siblings.
J Pediatr. 1968 Mar;72(3):377-83. No abstract available.
PMID: 5237795 [PubMed - indexed for MEDLINE]

64:  Roveta G.
 [Growth of transplanted Oberling myeloma in bone: fluorochromization with
acridine orange]
Boll Soc Ital Biol Sper. 1969 Oct 15;45(19):1233-4. Italian. No abstract
available.
PMID: 4990335 [PubMed - indexed for MEDLINE]

65:  Shen WF, Rozenfeld S, Kwong A, Kom ves LG, Lawrence HJ, Largman C.
 HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells.
Mol Cell Biol. 1999 Apr;19(4):3051-61.
PMID: 10082572 [PubMed - indexed for MEDLINE]

66:  Kuto F, Nagaoka T, Watanabe Y, Hayashi M, Horasawa Y, Hirasawa Y, Tokuhiro
H.
 Chronic myelocytic leukemia: ultrastructural histopathology of bone marrow from
patients in the chronic phase.
Ultrastruct Pathol. 1984;6(4):307-17.
PMID: 6592869 [PubMed - indexed for MEDLINE]

67:  Bijl JJ, van Oostveen JW, Walboomers JM, Brink AT, Vos W, Ossenkoppele GJ,
Meijer CJ.
 Differentiation and cell-type-restricted expression of HOXC4, HOXC5 and HOXC6
in myeloid leukemias and normal myeloid cells.
Leukemia. 1998 Nov;12(11):1724-32.
PMID: 9823947 [PubMed - indexed for MEDLINE]

68:  Popova EY, Claxton DF, Lukasova E, Bird PI, Grigoryev SA.
 Epigenetic heterochromatin markers distinguish terminally differentiated
leukocytes from incompletely differentiated leukemia cells in human blood.
Exp Hematol. 2006 Apr;34(4):453-62.
PMID: 16569592 [PubMed - indexed for MEDLINE]

69:  Ackerman GA.
 Localization of pyroantimonate-precipitable cation and surface coat anionic
binding sites in developing erythrocytic cells and macrophages in normal human
bone marrow.
Z Zellforsch Mikrosk Anat. 1972;134(2):153-66. No abstract available.
PMID: 4119478 [PubMed - indexed for MEDLINE]

70:  Kaihotsu N.
 Electron microscopic studies on the maturation process of neutrophilic
leukocytes.
Kobe J Med Sci. 1967 Mar;13(1):47-66. No abstract available.
PMID: 5235561 [PubMed - indexed for MEDLINE]

71:  Liedeman RR, Matveyeva NP, Vostricova SA, Prilipko LL.
 Extrinsic factors affecting the binding of acridine orange to the DNP complex
of cell nuclei in different physiological states.
Exp Cell Res. 1975 Jan;90(1):105-10. No abstract available.
PMID: 47293 [PubMed - indexed for MEDLINE]

72:  Reiner P, Mardiak J, Reinerova M, Ujhazy V.
 Inhibition of colony-forming cells from bone marrow of leukemic patients by
3-oxauracil.
Neoplasma. 1981;28(5):533-9.
PMID: 6947140 [PubMed - indexed for MEDLINE]

73:  Oara K.
 [Studies on DNA content in human leukemic cells in bone marrow with
chemotherapy using the microspectrophotometer]
Nippon Ketsueki Gakkai Zasshi. 1970 Aug;33(4):363-81. Japanese. No abstract
available.
PMID: 5534615 [PubMed - indexed for MEDLINE]

74:  Lampert F.
 Attachment of human chromatin fibers to the nuclear membrane, as seen by
electron microscopy.
Humangenetik. 1971;13(4):285-95. No abstract available.
PMID: 5135848 [PubMed - indexed for MEDLINE]

75:  Vinogradova OA, Savchenko VG, Domracheva EV, Parovichnikova EN, Diachenko
LV, Alimova GA, Mendeleeva LP, Liubimova LS, Sokolov AN, Zhelnova EI,
Pokrovskaia OS.
 [Is leukemic transformation of donor cells possible?]
Ter Arkh. 2004;76(7):28-34. Russian.
PMID: 15379124 [PubMed - indexed for MEDLINE]

76:  Burgio GR, Severi F, Genova R.
 [Use of fluorescence technics in the study of leukemic cells]
Minerva Pediatr. 1966 Jun 2;18(18):928-33. Italian. No abstract available.
PMID: 5990831 [PubMed - indexed for MEDLINE]

77:  Ernst P, Killmann SA.
 Effect of anti-leukemic drugs on cell cycle of human leukemic blast cells in
vivo.
Acta Med Scand. 1969 Sep;186(3):239-40. No abstract available.
PMID: 5363502 [PubMed - indexed for MEDLINE]

78:  Terzakis JA, Taskin M.
 Bone marrow leukemias and lymphoproliferative disorders: scanning electron
microscope diagnosis.
Ultrastruct Pathol. 2002 May-Jun;26(3):143-52.
PMID: 12184372 [PubMed - indexed for MEDLINE]

79:  Lowenberg B, van Putten WL, Touw IP, Delwel R, Santini V.
 Autonomous proliferation of leukemic cells in vitro as a determinant of
prognosis in adult acute myeloid leukemia.
N Engl J Med. 1993 Mar 4;328(9):614-9.
PMID: 8429853 [PubMed - indexed for MEDLINE]

80:  Litwin C, Leong KG, Zapf R, Sutherland H, Naiman SC, Karsan A.
 Role of the microenvironment in promoting angiogenesis in acute myeloid
leukemia.
Am J Hematol. 2002 May;70(1):22-30.
PMID: 11994978 [PubMed - indexed for MEDLINE]

81:  Orazi A, Kahsai M, John K, Neiman RS.
 p53 overexpression in myeloid leukemic disorders is associated with increased
apoptosis of hematopoietic marrow cells and ineffective hematopoiesis.
Mod Pathol. 1996 Jan;9(1):48-52.
PMID: 8821956 [PubMed - indexed for MEDLINE]

82:  Smetana K, Vlastiborova A, Iscenko I.
 Studies on micronucleoli of immature human leukemic neutrophils.
Neoplasma. 1973 May;20(5):491-8. No abstract available.
PMID: 4127832 [PubMed - indexed for MEDLINE]

83:  Matveeva NP, Lideman RR.
 [Effect of acid extraction of basic proteins on the binding of acridine orange
by cell chromatin]
Tsitologiia. 1975 Apr;17(4):432-6. Russian.
PMID: 1145760 [PubMed - indexed for MEDLINE]

84:  Hawley RG, Fong AZ, Ngan BY, de Lanux VM, Clark SC, Hawley TS.
 Progenitor cell hyperplasia with rare development of myeloid leukemia in
interleukin 11 bone marrow chimeras.
J Exp Med. 1993 Oct 1;178(4):1175-88.
PMID: 8104229 [PubMed - indexed for MEDLINE]

85:  Green D, Tew KD, Hisamatsu T, Schein PS.
 Correlation of nitrosourea murine bone marrow toxicity with deoxyribonucleic
acid alkylation and chromatin binding sites.
Biochem Pharmacol. 1982 May 1;31(9):1671-9.
PMID: 7104031 [PubMed - indexed for MEDLINE]

86:  Faber LM, van der Hoeven J, Goulmy E, Hooftman-den Otter AL, van
Luxemburg-Heijs SA, Willemze R, Falkenburg JH.
 Recognition of clonogenic leukemic cells, remission bone marrow and
HLA-identical donor bone marrow by CD8+ or CD4+ minor histocompatibility
antigen-specific cytotoxic T lymphocytes.
J Clin Invest. 1995 Aug;96(2):877-83.
PMID: 7635982 [PubMed - indexed for MEDLINE]

87:  Gil S, Luno E, Rodriguez JA.
 Acute myeloblastic leukemia with trilineage myelodysplasia and CD34+ blast
cells with abnormal chromatin clumping.
Haematologica. 1998 Aug;83(8):750-1.
PMID: 9793262 [PubMed - indexed for MEDLINE]

88:  Newman A, Clutterbuck RD, DeLord C, Powles RL, Catovsky D, Millar JL.
 The sensitivity of leukemic bone marrow to simvastatin is lost at remission: a
potential purging agent for autologous bone marrow transplantation.
J Investig Med. 1995 Jun;43(3):269-74.
PMID: 7614073 [PubMed - indexed for MEDLINE]

89:  Schumacher HR, McFeely AE, Davis KD, Maugel TK.
 The acute leukemic cell. IV. DNA synthesis in peripheral blood and bone marrow.
Am J Clin Pathol. 1971 Oct;56(4):508-14. No abstract available.
PMID: 5286506 [PubMed - indexed for MEDLINE]

90:  Denkers IA, de Jong-de Boer TJ, Beelen RH, Ossenkoppele GJ, Nauta JJ,
Langenhuijsen MM.
 Adhesive capacity of human long-term bone marrow cultures from normals and
patients with acute myeloid leukaemia: the influence of adhesion molecules.
Leuk Res. 1993 Mar;17(3):255-61.
PMID: 8450674 [PubMed - indexed for MEDLINE]

91:  Sievers EL, Lange BJ, Buckley JD, Smith FO, Wells DA, Daigneault-Creech CA,
Shults KE, Bernstein ID, Loken MR.
 Prediction of relapse of pediatric acute myeloid leukemia by use of
multidimensional flow cytometry.
J Natl Cancer Inst. 1996 Oct 16;88(20):1483-8.
PMID: 8841024 [PubMed - indexed for MEDLINE]

92:  Linssen P, Brons P, Knops G, Wessels H, de Witte T.
 Plasma and cellular pharmacokinetics of m-AMSA related to in vitro toxicity
towards normal and leukemic clonogenic bone marrow cells (CFU-GM, CFU-L).
Eur J Haematol. 1993 Mar;50(3):149-54.
PMID: 8472810 [PubMed - indexed for MEDLINE]

93:  Islam A, Catovsky D, Galton DA.
 Histological study of bone marrow regeneration following chemotherapy for acute
myeloid leukaemia and chronic granulocytic leukaemia in blast transformation.
Br J Haematol. 1980 Aug;45(4):535-40. No abstract available.
PMID: 7000152 [PubMed - indexed for MEDLINE]

94:  Sakagami H, Takahashi H, Yoshida H, Yamamura M, Fukuchi K, Gomi K,
Motohashi N, Takeda M.
 Induction of DNA fragmentation in human myelogenous leukaemic cell lines by
phenothiazine-related compounds.
Anticancer Res. 1995 Nov-Dec;15(6B):2533-40.
PMID: 8669819 [PubMed - indexed for MEDLINE]

95:  Tanaka M.
 Recombinant GM-CSF modulates the metabolism of cytosine arabinoside in leukemic
cells in bone marrow.
Leuk Res. 1993 Jul;17(7):585-92.
PMID: 8326741 [PubMed - indexed for MEDLINE]

96:  Hara H, Moriki T, Matsusaki K, Hiroi M, Yamane T.
 Electron microscopic localization of acridine orange binding to DNA within
various human brain tumor cells.
Acta Pathol Jpn. 1984 Sep;34(5):1041-7.
PMID: 6507086 [PubMed - indexed for MEDLINE]

97:  Preisler HD, Darzynkiewicw Z.
 Characterization of proliferative and quiescent leukemic cells by flow
cytometry.
J Med. 1981;12(6):415-25.
PMID: 6948070 [PubMed - indexed for MEDLINE]

98:  Manteifel' VM, Epifanova OR, Zelenin AV.
 [Electron microscopic morphometric study of activated chromatin of lymphocytes.
I. Variation of chromatin condensations during early action of
phytohemagglutinin]
Mol Biol (Mosk). 1982 Sep-Oct;16(5):1051-62. Russian.
PMID: 7144750 [PubMed - indexed for MEDLINE]

99:  Shaker S, Bernstein M, Momparler LF, Momparler RL.
 Preclinical evaluation of antineoplastic activity of inhibitors of DNA
methylation (5-aza-2'-deoxycytidine) and histone deacetylation (trichostatin A,
depsipeptide) in combination against myeloid leukemic cells.
Leuk Res. 2003 May;27(5):437-44.
PMID: 12620295 [PubMed - indexed for MEDLINE]

100:  Campbell GL, Gledhill BL.
 Chromatin of primitive erythroid cells from the chick embryo. I. Changes in
acridine orange binding and the sensitivity to the thermal denaturation during
maturation.
Chromosoma. 1973 Apr 27;41(4):385-94. No abstract available.
PMID: 4127018 [PubMed - indexed for MEDLINE]

101:  Bendall LJ, Bradstock KF, Gottlieb DJ.
 Expression of CD44 variant exons in acute myeloid leukemia is more common and
more complex than that observed in normal blood, bone marrow or CD34+ cells.
Leukemia. 2000 Jul;14(7):1239-46.
PMID: 10914548 [PubMed - indexed for MEDLINE]

102:  Court EL, Davidson K, Smith MA, Inman L, Marriott SA, Smith JG, Pallister
CJ.
 C-kit mutation screening in patients with acute myeloid leukaemia: adaptation
of a Giemsa-stained bone-marrow smear DNA extraction technique.
Br J Biomed Sci. 2001;58(2):76-84.
PMID: 11440210 [PubMed - indexed for MEDLINE]

103:  Marcucci G, Strout MP, Bloomfield CD, Caligiuri MA.
 Detection of unique ALL1 (MLL) fusion transcripts in normal human bone marrow
and blood: distinct origin of normal versus leukemic ALL1 fusion transcripts.
Cancer Res. 1998 Feb 15;58(4):790-3.
PMID: 9485036 [PubMed - indexed for MEDLINE]

104:  Schumacher HR, McFeely AE, Davis KD, Maugel TK.
 The acute leukemic cell. V. RNA synthesis in peripheral blood and bone marrow.
Am J Med Sci. 1971 Dec;262(6):327-32. No abstract available.
PMID: 5291592 [PubMed - indexed for MEDLINE]

105:  Holle M.
 [Vitality studies in bone marrow cells by means of fluorescence microscopy]
Folia Haematol Int Mag Klin Morphol Blutforsch. 1978;105(1):66-70. German.
PMID: 77821 [PubMed - indexed for MEDLINE]

106:  Gabius S, Wawotzny R, Martin U, Wilholm S, Gabius HJ.
 Carbohydrate-dependent binding of human myeloid leukemia cell lines to
neoglycoenzymes, matrix-immobilized neoglycoproteins, and bone marrow stromal
cell layers.
Ann Hematol. 1994 Mar;68(3):125-32.
PMID: 8167178 [PubMed - indexed for MEDLINE]

107:  Evenson DP, Traganos F, Darzynkiewicz Z, Staiano-Coico L, Melamed MR.
 Effects of 9,10-anthracenedione,
1,4-bis[[2-[(2-hydroxyethyl)amino]-ethyl]amino]-, diacetate on cell morphology
and nucleic acids of friend leukemia cells.
J Natl Cancer Inst. 1980 Apr;64(4):857-66.
PMID: 6928997 [PubMed - indexed for MEDLINE]

108:  Beran M, Pisa P, Kantarjian H, Porwit A, Bjorkholm M.
 Growth of sensitive and drug-resistant human myeloid leukemia cells in SCID
mice.
Hematol Pathol. 1994;8(4):135-54.
PMID: 7860433 [PubMed - indexed for MEDLINE]

109:  Milner GR.
 Changes in chromatin structure during interphase in human normoblasts.
Nature. 1969 Jan 4;221(5175):71-2. No abstract available.
PMID: 5782619 [PubMed - indexed for MEDLINE]

110:  Bast RC Jr, Ritz J, Lipton JM, Feeney M, Sallan SE, Nathan DG, Schlossman
SF.
 Elimination of leukemic cells from human bone marrow using monoclonal antibody
and complement.
Cancer Res. 1983 Mar;43(3):1389-94.
PMID: 6337707 [PubMed - indexed for MEDLINE]
 

111:  Kusuzaki K, Murata H, Takeshita H, Hashiguchi S, Nozaki T, Emoto K,
Ashihara T, Hirasawa Y.
 Intracellular binding sites of acridine orange in living osteosarcoma cells.
Anticancer Res. 2000 Mar-Apr;20(2A):971-5.
PMID: 10810383 [PubMed - indexed for MEDLINE]

112:  Smith FO, Rauch C, Williams DE, March CJ, Arthur D, Hilden J, Lampkin BC,
Buckley JD, Buckley CV, Woods WG, Dinndorf PA, Sorensen P, Kersey J, Hammond D,
Bernstein ID.
 The human homologue of rat NG2, a chondroitin sulfate proteoglycan, is not
expressed on the cell surface of normal hematopoietic cells but is expressed by
acute myeloid leukemia blasts from poor-prognosis patients with abnormalities of
chromosome band 11q23.
Blood. 1996 Feb 1;87(3):1123-33.
PMID: 8562938 [PubMed - indexed for MEDLINE]

113:  Frank GM, Karnaukhov VN, Kolaev VA, Iashin VA.
 [Spectral characteristics of human white blood cells fluorochromed with
acridine orange]
Biofizika. 1977 Nov-Dec;22(6):1015-23. Russian.
PMID: 73388 [PubMed - indexed for MEDLINE]

114:  Losecke W, Kerkis AJ, Linss W, Geyer G.
 DNase--a likely probe of juxtatranscriptional DNP.
Acta Histochem. 1980;67(1):22-7.
PMID: 6160713 [PubMed - indexed for MEDLINE]

115:  Makrynikola V, Bianchi A, Bradstock K, Gottlieb D, Hewson J.
 Migration of acute lymphoblastic leukemia cells into human bone marrow stroma.
Leukemia. 1994 Oct;8(10):1734-43.
PMID: 7523799 [PubMed - indexed for MEDLINE]

116:  Koeffler HP, Amatruda T, Ikekawa N, Kobayashi Y, DeLuca HF.
 Induction of macrophage differentiation of human normal and leukemic myeloid
stem cells by 1,25-dihydroxyvitamin D3 and its fluorinated analogues.
Cancer Res. 1984 Dec;44(12 Pt 1):5624-8.
PMID: 6594194 [PubMed - indexed for MEDLINE]

117:  Gerdes J, Marathe RL, Bloodworth JM, MacKinney AA Jr.
 Gaucher cells in chronic granulocytic leukemia.
Arch Pathol. 1969 Aug;88(2):194-8. No abstract available.
PMID: 5256058 [PubMed - indexed for MEDLINE]

118:  Soede RD, Wijnands YM, Kamp M, van der Valk MA, Roos E.
 Gi and Gq/11 proteins are involved in dissemination of myeloid leukemia cells
to the liver and spleen, whereas bone marrow colonization involves Gq/11 but not
Gi.
Blood. 2000 Jul 15;96(2):691-8.
PMID: 10887136 [PubMed - indexed for MEDLINE]

119:  Islam A, Catovsky D, Goldman JM, Galton DA.
 Histomorphological study of cellular interactions between stromal and
haemopoietic stem cells in normal and leukaemic bone marrow.
Histopathology. 1984 Mar;8(2):293-313.
PMID: 6586632 [PubMed - indexed for MEDLINE]

120:  Ohashi T, Kusuhara S.
 Immunoelectron microscopic detection of estrogen target cells in the bone
marrow of estrogen-treated male Japanese quail.
Bone Miner. 1993 Jan;20(1):31-9.
PMID: 8453320 [PubMed - indexed for MEDLINE]

121:  Coulombel L, Eaves CJ, Dube ID, Kalousek DK, Eaves AC.
 Variable persistence of leukemic progenitor cells in long-term CML and AML
marrow cultures.
Kroc Found Ser. 1984;18:243-54. No abstract available.
PMID: 6597867 [PubMed - indexed for MEDLINE]

122:  Fischbach NA, Rozenfeld S, Shen W, Fong S, Chrobak D, Ginzinger D, Kogan
SC, Radhakrishnan A, Le Beau MM, Largman C, Lawrence HJ.
 HOXB6 overexpression in murine bone marrow immortalizes a myelomonocytic
precursor in vitro and causes hematopoietic stem cell expansion and acute
myeloid leukemia in vivo.
Blood. 2005 Feb 15;105(4):1456-66. Epub 2004 Nov 2.
PMID: 15522959 [PubMed - indexed for MEDLINE]

123:  Baersch G, Mollers T, Hotte A, Dockhorn-Dworniczak B, Rube C, Ritter J,
Jurgens H, Vormoor J.
 Good engraftment of B-cell precursor ALL in NOD-SCID mice.
Klin Padiatr. 1997 Jul-Aug;209(4):178-85.
PMID: 9293448 [PubMed - indexed for MEDLINE]

124:  Schumann RR, Nakarai T, Gruss HJ, Brach MA, von Arnim U, Kirschning C,
Karawajew L, Ludwig WD, Renauld JC, Ritz J, Herrmann F.
 Transcript synthesis and surface expression of the interleukin-2 receptor
(alpha-, beta-, and gamma-chain) by normal and malignant myeloid cells.
Blood. 1996 Mar 15;87(6):2419-27.
PMID: 8630406 [PubMed - indexed for MEDLINE]

125:  Mamaev NN, Mamaeva SE, Liburkina IL, Kozlova TV, Medvedeva NV.
 [Nucleolar organizer activity of normal and leukemic cells in human bone
marrow]
Tsitologiia. 1984 Jan;26(1):46-51. Russian.
PMID: 6583880 [PubMed - indexed for MEDLINE]

126:  Esa A, Edelmann P, Kreth G, Trakhtenbrot L, Amariglio N, Rechavi G,
Hausmann M, Cremer C.
 Three-dimensional spectral precision distance microscopy of chromatin
nanostructures after triple-colour DNA labelling: a study of the BCR region on
chromosome 22 and the Philadelphia chromosome.
J Microsc. 2000 Aug;199(Pt 2):96-105.
PMID: 10947902 [PubMed - indexed for MEDLINE]

127:  Georgii A, Vykoupil KF, Thiele J.
 Chronic megakaryocytic granulocytic myelosis-CMGM. A subtype of chronic myeloid
leukemia.
Virchows Arch A Pathol Anat Histol. 1980;389(3):253-68.
PMID: 6935864 [PubMed - indexed for MEDLINE]

128:  Schmetzer HM, Braun S, Wiesner D, Duell T, Gerhartz HH, Mittermueller J.
 Gene rearrangements in bone marrow cells of patients with acute myelogenous
leukemia.
Acta Haematol. 2000;103(3):125-34.
PMID: 10940650 [PubMed - indexed for MEDLINE]

129:  Ghannadan M, Wimazal F, Simonitsch I, Sperr WR, Mayerhofer M, Sillaber C,
Hauswirth AW, Gadner H, Chott A, Horny HP, Lechner K, Valent P.
 Immunohistochemical detection of VEGF in the bone marrow of patients with acute
myeloid leukemia. Correlation between VEGF expression and the FAB category.
Am J Clin Pathol. 2003 May;119(5):663-71.
PMID: 12760284 [PubMed - indexed for MEDLINE]

130:  Matveeva NP, Lideman RR.
 [Binding of acridine orange by chromatin in human lymphocytes with different
capabilities for adhesion]
Tsitologiia. 1975 Jun;17(6):731-4. Russian.
PMID: 1154501 [PubMed - indexed for MEDLINE]

131:  Joling P, Rademakers LH, Verdaasdonk MA, Zimmermann D, Spierings DC,
Werner N, de Weger RA, van den Tweel JC.
 Interaction of tumour cells with cultured stromal cells from human bone marrow.
Thymus. 1994;23(2):115-26.
PMID: 7536964 [PubMed - indexed for MEDLINE]

132:  Maeda T, Kosugi S, Ujiie H, Osumi K, Fukui T, Yoshida H, Kashiwagi H,
Ishikawa J, Tomiyama Y, Matsuzawa Y.
 Localized relapse in bone marrow in a posttransplantation patient with t(6;9)
acute myeloid leukemia.
Int J Hematol. 2003 Jun;77(5):522-5.
PMID: 12841393 [PubMed - indexed for MEDLINE]

133:  Thiele J, Vykoupil KF, Georgii A.
 Myeloid dysplasia (MD): a hematological disorder preceding acute and chronic
myeloid leukemia. A morphological study on sequential core biopsies of the bone
marrow in 27 patients.
Virchows Arch A Pathol Anat Histol. 1980;389(3):343-67. No abstract available.
PMID: 6935868 [PubMed - indexed for MEDLINE]

134:  Krenacs T, Rosendaal M.
 Connexin43 gap junctions in normal, regenerating, and cultured mouse bone
marrow and in human leukemias: their possible involvement in blood formation.
Am J Pathol. 1998 Apr;152(4):993-1004.
PMID: 9546360 [PubMed - indexed for MEDLINE]

135:  Koeffler HP, Lowe L, Golde DW.
 Amygdalin (Laetrile): effect on clonogenic cells from human myeloid leukemia
cell lines and normal human marrow.
Cancer Treat Rep. 1980 Jan;64(1):105-9.
PMID: 6929726 [PubMed - indexed for MEDLINE]

136:  Gallo JH, Ordonez JV, Brown GE, Testa JR.
 Synchronization of human leukemic cells: relevance for high-resolution
chromosome banding.
Hum Genet. 1984;66(2-3):220-4.
PMID: 6585345 [PubMed - indexed for MEDLINE]

137:  Leuschner U, Hill K, Semmler U.
 [Pathomorphology of acute hypoxic bone marrow damage. Electron microscopy
findings on erythroblasts from rabbit bone marrow following 2 hours of ischemia]
Blut. 1973 Jul;27(1):44-53. German. No abstract available.
PMID: 4718813 [PubMed - indexed for MEDLINE]

138:  Dzhanimanov NB, Makhatadze IK, Chikhladze MSh, Monaselidze DR,
Sheklashvili MSh.
 [Research on bone marrow cells in leukemias using microcalorimetric and
autoradiographic methods]
Gematol Transfuziol. 1988 Mar;33(3):58-60. Russian. No abstract available.
PMID: 3384303 [PubMed - indexed for MEDLINE]

139:  Fredericq E, Houssier C.
 Study of the interaction of DNA and acridine orange by various optical methods.
Biopolymers. 1972;11(11):2281-308. No abstract available.
PMID: 4634867 [PubMed - indexed for MEDLINE]

140:  Pakesch F, Pietschmann H.
 [On the electron microscopic description of the ATP-splitting enzyme activity
in bone marrow cells]
Blut. 1967 Mar;14(6):348-50. German. No abstract available.
PMID: 4225678 [PubMed - indexed for MEDLINE]

141:  Clayton DA, Vinograd J.
 Complex mitochondrial DNA in leukemic and normal human myeloid cells.
Proc Natl Acad Sci U S A. 1969 Apr;62(4):1077-84. No abstract available.
PMID: 5256408 [PubMed - indexed for MEDLINE]

142:  Tanaka Y.
 An electron microscopic study of non-phagocytic reticulum cells in human bone
marrow. I. Cells with intracytoplasmic fibrils.
Nippon Ketsueki Gakkai Zasshi. 1969 Apr;32(2):275-86. No abstract available.
PMID: 4981405 [PubMed - indexed for MEDLINE]

143:  Faller A.
 [Electron microscopic studies on the maturation of the eosinophilic granula in
the bone marrow of the horse]
Verh Anat Ges. 1971;65:63-8. German. No abstract available.
PMID: 4947861 [PubMed - indexed for MEDLINE]

144:  Demaree RS Jr, Marquardt WC.
 Avian trypanosome division; a light and electron microscope study.
J Protozool. 1971 Aug;18(3):388-91. No abstract available.
PMID: 5132314 [PubMed - indexed for MEDLINE]

145:  Alvarez MR, Reyniers JP.
 Microspectrofluorometric comparison of acridine orange dye binding in
meristematic and parenchymal nuclei of the orchid embryo.
Exp Cell Res. 1970 Aug;61(2):326-32. No abstract available.
PMID: 4195912 [PubMed - indexed for MEDLINE]

146:  Clayton DA, Davis RW, Vinograd J.
 Homology and structural relationships between the dimeric and monomeric
circular forms of mitochondrial DNA from human leukemic leukocytes.
J Mol Biol. 1970 Jan 28;47(2):137-53. No abstract available.
PMID: 5265062 [PubMed - indexed for MEDLINE]

147:  DeCarvalho S.
 Epigenetic transformation by RNA from human neoplastic cells.
Oncology. 1973;27(1):3-29. Review. No abstract available.
PMID: 4566134 [PubMed - indexed for MEDLINE]

148:  Machino M, Shimamura Y.
 Letter: Labyrinth structure in the human leukemic myelocytes.
J Electron Microsc (Tokyo). 1973;22(1):103-4. No abstract available.
PMID: 4776960 [PubMed - indexed for MEDLINE]

149:  Morgenstern E, Werner G, Neumann K, Hufnagl D.
 [Freeze ultramicrotomy of bone marrow]
Blut. 1973 Apr;26(4):250-60. German. No abstract available.
PMID: 4700224 [PubMed - indexed for MEDLINE]

150:  Pushkar' NS, Itkin IuA, Koz'min IuV, Rozanov LF.
 [Microscopic and x-ray structural studies of crystallization processes during
the freezing of biological objects]
Biofizika. 1973 Mar-Apr;18(2):389-91. Russian. No abstract available.
PMID: 4701450 [PubMed - indexed for MEDLINE]

151:  Adams LR, Kamentsky LA.
 Machine characterization of human leukocytes by acridine orange fluorescence.
Acta Cytol. 1971 May-Jun;15(3):289-91. No abstract available.
PMID: 5283474 [PubMed - indexed for MEDLINE]

152:  Zeve VH, Lucas LS, Manaker RA.
 Continuous cell culture from a patient with chronic myelogenous leukemia. II.
Detection of a herpes-like virus by electron microscopy.
J Natl Cancer Inst. 1966 Dec;37(6):761-73. No abstract available.
PMID: 5225151 [PubMed - indexed for MEDLINE]

153:  Tavassoli M, Crosby WH.
 Fate of the nucleus of the marrow erythroblast.
Science. 1973 Mar 2;179(76):912-3. No abstract available.
PMID: 4687788 [PubMed - indexed for MEDLINE]

154:  Bogomolov KS, Razorenova IF, Khruleva LS, Kozinets GI, Telelenova NN.
 [Autoradiographic method in the electron microscopic studies]
Lab Delo. 1971;6:359-62. Russian. No abstract available.
PMID: 4108753 [PubMed - indexed for MEDLINE]

155:  Vitagliano V, Costantino L, Zagari A.
 Interaction between acridine orange and poly(styrenesulfonic acid).
J Phys Chem. 1973 Jan 18;77(2):204-10. No abstract available.
PMID: 4683216 [PubMed - indexed for MEDLINE]

156:  Zinner K, Cilento G.
 Extrinsic Cotton effects of acridine orange bound to helical sodium
desoxycholate.
Biopolymers. 1972;11(7):1521-5. No abstract available.
PMID: 5042853 [PubMed - indexed for MEDLINE]

157:  Laerum OD, Aardal NP, Mork SJ, Thorud E.
 [Clinical cytofluorometry]
Tidsskr Nor Laegeforen. 1977 Sep 10;97(25):1275-9. Norwegian. No abstract
available.
PMID: 905997 [PubMed - indexed for MEDLINE]