Bone-marrow cells from patients with acute leukemia in remission were tested for their capacity to produce a substance (leukemia-associated inhibitory activity, LIA) that inhibits the formation of granulocyte and macrophage colonies in cultures of normal, but not of leukemic, bone marrow. LIA was detected in extracts of whole marrow in only eight of 83 patients in remission. However, extracts of slowly sedimenting cells, separated by velocity sedimentation from the marrows of eight patients in remission whose whole marrow had produced no LIA, produced inhibitory material in all cases. Extracts of the more rapidly sedimenting cells from these marrows contained an inactivator of LIA. Three of six patients in remission whose unfractionated marrow was unresponsive to LIA had a subpopulation of colony-forming cells that was sensitive to the inhibitor. These observations suggest that certain cellular functions do not completely return to normal during remission of acute leukemia. (N Engl J Med 301:346–351, 1979) WE have recently reported an in vitro cellular inhibitory phenomenon that may provide an explanation for the suppression of normal hematopoiesis associated with acute leukemia and that may have a role in the proliferative advantage leukemia cells appear to have over normal cells.1,2 Cell extracts and culture medium conditioned by cells from bone marrow, spleen or blood of patients with acute leukemia in relapse consistently inhibited the cells from bone marrows of normal donors that formed colonies of granulocytes and macrophages. This cell-derived inhibitory substance (leukemia-associated inhibitory activity, LIA) was specific for colony-forming cells while they were synthesizing DNA.1,3 In.
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