Evidence for a Proliferative Advantage of Human Leukemia Colony-Forming Cells In Vitro 23

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Abstract
Inhibitory mechanisms that might provide leukemia granulocytic stem cells with a proliferative advantage over normal granulocytic stem cells were investigated. Extracts from marrow and blood cells of patients with leukemia were assayed for inhibitory activity against the exogenously stimulated cloning of normal and leukemia granulocyte—monocyte colony-forming cells in agar (CFU-C) present in fractions of nonadherent light density bone marrow. Extracts of cells from patients who had acute leukemia not in remission and who had inhibitory activity containing cells had higher levels of inhibitory activity against normal CFU-C than did extracts from cells of patients who had chronic leukemia. Extracts from normal cells did not inhibit exogenously stimulated normal or leukemia colony formation. Leukemia CFU-C were unaffected by single or multiple additions of leukemia cell extracts containing 104-106 times as much inhibitory activity as that necessary for maximal inhibition of CFU-C from normal donors. Cells from patients with acute leukemia in remission rarely demonstrated inhibitory activity. However, CFU-C from most of these patients with acute leukemia in remission were insensitive to active leukemia cell extracts. The cell responsible for inhibitory activity against normal CFU-C was nonadherent and of light density and had a velocity sedimentation range of 2.5–6.3 mm/hour. The number and percent of cells containing inhibitory activity varied from patient to patient but appeared to be higher in patients with more aggressive disease. inhibitory cells could be partially separated from CFU-C of leukemia patients. These in vitro phenomena may have relevance to the pathogenesis of acute leukemia.