Presented at the 63rd Annual Meeting of the
American Association for Cancer Research, and published in Proc. Am. Assoc.
Cancer Research, vol. 13, p. 108 (1972):
"Cytogenetic and Ultrastructural Evidence of Altered
DNA Metabolism in Leukemic Cells",
Michael J. Ahearn and Jose M. Trujillo,
M.D. Anderson Institute
Houston, Texas 77025
Abstract:
We have previously reported a correlation in the occurrence of abnormal
cytogenetic clones and ultrastructural nuclear blebs in the hematpoietic
tissue of approximately 41% of acute leukemias presenting at this institution
in active disease. Both abnormalities are found to disappear when a patient
achieves remission only to reappear at the time of relapse. Since structures
morphologically similar to this nuclear bleb have been attributed to DNA
inhibiting drug therapy we have examined the leukemic associated nuclear
blebbed and aneuploid cell for evidence of altered DNA synthesis. Autoradiographic
techniques at the light and electron microscope level were used to measure
H3-thymidine uptake in these cells. Frenster's technique has
been employed to delineate the active extended euchromatin portion of the
cell nucleus (Cancer Research 31: 1128
(1971). These studies have revealed a reduced rate of H3-thymidine
uptake by the chromosomes of the abnormal clone cells as opposed to those
comprising the diploid component of the patients bone marrow. Likewise
at the ultrastructural level cells bearing nuclear blebs representing the
aneuploid clone incorporate H3-thymidine and stain with acridine
orange to a lesser degree than the non-blebbed diploid cells from the same
specimen. These studies offer presumptive evidence for a deranged DNA metabolism
in the aneuploid cell and have relevance in the interpretation of leukemic
kinetic data.
Additional Reference:
1. Frenster JH, "Electron Microscopic Localization of Acridine Orange
Binding to DNA within Human Leukemic Bone Marrow Cells", Cancer
Res. 31: 1128 (August, 1971).