INHIBITION BY ARABINOSYLCYTOSINE OF DNA-SYNTHESIS IN BONE MARROWS OF RELAPSED AML PATIENTS

This study was designed to examine whether the selective pressure of intermittent araC maintenance therapy in AML was sufficient for the selection of cells, in either the myeloid or erythroid lines, in which araC was no longer capable of inhibiting DNA synthesis as evidenced by labelled thymidine incorporation. Nucleated cells from bone marrow aspirations were exposed to araC for 1 hr prior to addition of tritiated thymidine. Grain counts on radioautograms were determined either visually or photometrically. In only 1 of 12 patients examined was there evidence of myeloblasts in which in vitro DNA synthesis was relatively unaffected by araC. In the remaining patients there was no evidence for the emegence of myeloblast or erythroid precursor populations in which araC did not inhibit DNA synthesis. DNA synthesis in the more differentiated myeloid precursors appeared less sensitive to inhibition by araC. It would thus appear that in 11 of the 12 AML patients studied the inability to clinically control the disease with araC is not due to biochemical changes related to araC transport, phosphorylation or the ability of araC triphosphate to inhibit DNA synthesis. © 1979.