SUPPRESSION OF NORMAL HEMATOPOIESIS IN ACUTE-LEUKEMIA - EFFECT OF LEUKEMIC-CELLS ON BONE-MARROW STROMAL CELLS AND HEMATOPOIETIC PROGENITOR CELLS

Effects of leukemic cells (LC) on bone marrow stromal cells and myeloi d progenitor cells (CFU-C) were studied in vitro, using LC lines with different lineage characteristics. LC and/or LC-conditioned medium (LC -CM) inhibited the growth of a stromal cell line, KM-101, and adherent cells of a long-term bone marrow culture (LTBMC) established from nor mal bone marrow. The inhibition was more prominent when LC were cocult ured directly with KM-101 cells than when LC were cultured separate fr om the KM-101 cell layer via membrane filtration, or when LC-CM was ad ded to KM-101 cells or LTBMC. LC-CM also exerted an inhibitory effect on the ability of LTBMC adherent cells to bind CFU-C. Furthermore, LC- CM inhibited the growth and survival of early and late CFU-C, but not the growth of LC. All these inhibitory effects were seen irrespective of the lineage characteristics of LC, but not seen with CM prepared fr om normal bone marrow immature granulocytes or peripheral blood lympho cytes. Neither tumor necrosis factor-alpha nor interferon-alpha was de tected in these LC-CM. These findings suggest that LC suppress normal hematopoiesis through the release of undefined substance(s) inhibiting the growth and/or survival of stromal cells and hemopoietic progenito r cells as well as the function of stromal cells.