Isolated Leukemic Cell Influence in Normal Hemic Colony Growth

Normal bone marrow hematopoiesis declines during the course of an experimental acute myelogenous leukemia in the rat. The reduction in the committed stem cell population occurs at a time which precedes any crowding-out effect of the expanding leukemic cell population. The present study is designed to assess the role of soluble factor(s) released by leukemic cells in the growth of normal erythrocytic and granulocytic precursors. Leukemic cells harvested from Shay chloroleukemic rats show continuous proliferation when grown in intraperitoneal diffusion chambers (DC). Bone marrow collected 6 days after chamber implantation demonstrated significant decreases in CFU-E numbers when assayed in vitro in plasma clot cultures. The in vivo plasma clot diffusion chamber (PCDC) culture system allows for the simultaneous growth of erythrocytic and granulocytic colonies. Bone marrow collected from leukemic-DC donor rats showed slightly elevated colony numbers when assayed in PCDC in normal recipients. However, when assays were performed in recipients containing an additional set of isolated leukemic-DC, hematopoietic colony growth was inhibited. Inhibition appeared to be directed to both the erythroid and myeloid line. The results indicate that isolated leukemic cells growing within a physiologic environment are capable of releasing soluble factors that over considerable distances have an inhibitory influence on the development of committed hematopoietic stem cells.