Studies of cellular proliferation in human leukemia. IV. Behavior of normal hematopoietic cells in 3 adults with acute leukemia given continuous infusions of 3 H‐thymidine for 8 or 10 days

Proliferative behavior of residual normal hematopoietic cells was studied in 3 patients with acute leukemia given continuous infusions of 3 H‐thymidine for 8 or 10 days. The erythrocyte precursors were reduced in number, but were dividing rapidly at about the same rate as reported in normal subjects (i.e., generation time about 1 day or less); this is significantly faster than the mean generation time of the labeled leukemic cells. The proliferative rate of the red cell precursors in 1 patient was not appreciably affected by thioguanine, although the drug caused a complete remission of the disease. The red cell precursors showed no significant impairment of maturation, but the data suggests that they may have undergone more divisions during passage through the several maturation compartments than occurs in the normal state. The main reason for deficient red cell production in acute leukemia appears to be that the leukemic cells somehow interfere with the activation of stem cells and, therefore, an insufficient number of pronormoblasts are formed; the mechanism of inhibition is unknown. The proliferative behavior of the earliest granulocyte precursors could not be determined and that of the myelocytes varied, being fastest in a patient who had an infection. Prednisone and thioguanine had little effect, but 5‐fluoro‐2′‐deoxyuridine slowed the proliferation of the granulocyte precursors more than that of the leukemic cells. Almost all granulocytes were labeled at the end of the infusions and the emergence times of labeled metamyelocytes and later forms were similar to those reported from normal subjects, indicating that their maturation process is not defective. None of the lymphocytes were labeled on short‐term in vitro incubation with 3 H‐thymidine, but appreciable numbers of both large and small lymphocytes were labeled at the end of the infusions. Their order of appearance in all patients suggests that most of the small lymphocytes originated in the marrow; in the one patient (S.W.), in whom large lymphocytes could be identified in both marrow and blood, the large cells apparently originated mostly in extramedullary sites. The cells identified as large or small lymphocytes in marrow and blood probably did not divide in these compartments; the exact proliferative rate of their precursors could not be determined, but it was appreciably slowed by chemotherapy.