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 myeloid 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 normal bone marrow. The inhibition was more prominent when LC were cocultured directly with KM-101 cells than when LC were cultured separate from the KM-101 cell layer via membrane filtration, or when LC-CM was added 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 from normal bone marrow immature granulocytes or peripheral blood lymphocytes. Neither tumor necrosis factor-alpha nor interferon-alpha was detected 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 progenitor cells as well as the function of stromal cells.
Aoyagi
M
M
Third Department of Internal Medicine, Dokkyo University School of Medicine, Tochigi.
Furusawa
S
S
Waga
K
K
Tsunogake
S
S
Shishido
H
H
D001853:Bone Marrow / Q000473:pathology*; D002448:Cell Adhesion; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003470:Culture Media; D017077:Culture Media, Conditioned; D005353:Fibronectins / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D007938:Leukemia / Q000473:pathology* / Q000503:physiopathology; D014407:Tumor Cells, Cultured / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003470:Culture Media; D017077:Culture Media, Conditioned; D005353:Fibronectins; D006131:Growth Inhibitors; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha