DNA polymerases in normal and leukemic human hematopoietic cells.

DNA polymerase activities were assayed in bone marrow cells and peripheral leukocytes from normal people and patients with acute myelogenous, chronic lymphocytic, and chronic myelogenous leukemia. Extracts of subcellular components were fractionated by velocity sedimentation through sucrose density gradients and assayed using activated DNA as template. Two major DNA-dependent DNA pelymerases were found in human cells with molecular weights of approximately 50,000 and 200,000 daltons, respectively. The DNA polymerase of high molecular weight is located in th soluble cytoplasmic fraction and is inhibited by N-ethylmaleimide. The low molecular weight polymerase is detected in extracts of nuclei and in the soluble fraction. It is resistant to inhibition by N-ethylmaleimide. In all cell types tested, total DNA pelymerase activities were much higher in cytoplasmic than in nuclear extracts. Lymphocytes purified from normal peripheral blood had three to four times as much of both the high and low molecular weight pelymerase activities per cell as purified granulocytes. Leukemic myeloblasts had 10 to 20 times as much cytoplasmic DNA pelymerase activity as more mature leukocytes from normal peripheral blood. In general, immature granulopeietic cells contained higher total DNA pelymerase activities than more mature granulocytes, and the major increases in pelymerase activities were in the high and low molecular weight cytoplasmic enzymes rather than in the nuclear enzyme.