Study of growth factor RNA levels in the stromal cells derived from the adherent layer of long-term bone marrow culture demonstrated constitutive expression of transforming growth factor β1 (TGF-β1) and macrophage colony-stimulating factor. These cells did not express granulocyte colony-stimulating factor, granulocyte-monocyte colony-stimulating factor, interleukin (IL) 1α, IL-1β, IL-3, and IL-6. However, granulocyte colony-stimulating factor expression could be induced by recombinant human IL-1β; while IL-6 could be induced by both IL-1β and tumor necrosis factor-α. No differences could be detected between adherent layers established from normal and benign phase Ph1 chronic myelogenous leukemia bone marrow. The uninduced expression of TGF-β1, a potent hematopoietic cell growth inhibitor, suggests that stromal cells play an inherent role in regulating the proliferation of adjacent bone marrow hematopoietic progenitor cells. However, a defect in stromal TGF-β1 production cannot account for the profoundly expanded myeloid compartment in chronic phase chronic myelogenous leukemia. In contrast to the constitutive expression of TGF-β1 and macrophage colony-stimulating factor, hematopoietic growth factors are only expressed following a proper stimulation.
Supported, in part, by the John D. and Catherine T. MacArthur Foundation, and Dalis Foundation. Research conducted, in part, by the Clayton Foundation for Research. Dr. Gutterman is a Senior Clayton Foundation Investigator.