Acidic Isoferritins as Feedback Regulators in Normal and Leukemic Myelopoiesis

Abstract

The absence of normal hematopoiesis during acute leukemia not in remission and the recovery of apparently normal blood cells during chemotherapy-induced remission suggest that suppressive cell interactions may be involved in the pathogenesis of acute leukemia. Others have shown inhibition of normal progenitor cell proliferation and differentiation by cells from patients with leukemia, but little or no information was provided regarding the actual characterization of the inhibitory cells or the mechanisms of action (Broxmeyer and Moore 1978). We have demonstrated the existence of an S-phase specific inhibitory activity [leukemia-associated inhibitory activity (LIA)] against normal granulocyte-macrophage progenitor cells (CFU-GM) which was produced by bone marrow, spleen, and blood cells from patients with acute and chronic myeloid and lymphoid leukemia and “preleukemia” (Broxmeyer et al. 1978a,b, 1979a,b). Greater concentrations of LIA were found during acute leukemia (newly diagnosed and untreated, or on therapy but not in remission) than during chronic leukemia (Broxmeyer et al. 1978a,b). Remission of acute leukemia was associated with low levels of LIA (Broxmeyer et al. 1978b, 1979a), and LIA at that time was not found in hemopoietic cells from normal donors (Broxmeyer et al. 1978a,b, 1979a,b). In contrast to its action on normal CFU-GM, LIA was not effective in suppressing the growth of normal CFU-GM from patients with acute leukemia who were not in remission and from many patients with acute leukemia during remission and with chronic leukemia (Broxmeyer et al. 1978b, 1979a,b). We postulated that LIA may thus confer a proliferative advantage to abnormally responsive cells (Broxmeyer et al. 1978b).

Supported by Public Health service grants CA 23528 and CA 08748 from the National Cancer Institute and by the Tumorzentrum Heidelberg-Mannheim, the H. Margolis Fund and the Gar Reichman Foundation