Studies of cellular proliferation in human leukemia.VI. The proliferative activity, generation time, and emergence time of neutrophilic granulocytes in chronic granulocytic leukemia

The proliferative kinetics of neutrophilic granulocytes were studied in 3 patients with typical chronic granulocytic leukemia (CGL) by means of differential counts, mitotic indexes, and 3H-thymidine labeling using autoradio-graphic methods. The granulocyte precursors in CGL had lower mitotic and 3H-thymidine labeling indexes than the corresponding normal cells; their median grain count halving times were longer than normal in 2 patients and approximately normal in the third. The proliferative rates appeared similar in the marrow and spleen but the cells rarely divided in the blood. In one patient given a continuous intravenous 3H-thymidine infusion for 10 days, 100% of the granulocyte precursors were labeled. The minimum maturation time of CGL neutrophilics was approximately normal, but their average transit times through the myelocyte and later maturation compartments was prolonged. The overproduction of granulocytes appears mainly due to increased formation of myeloblasts; whether this is due to an increased rate of stem cell activation or whether the myeloblasts may themselves function to some extent as selfsustaining cells is unknown.