ROLE OF CYTOKINES IN LEUKEMIC TYPE GROWTH OF MYELODYSPLASTIC CD34(+) CELLS

The clonal growth of progenitor cells from myelodysplastic syndromes ( MDS) can be subdivided into four growth patterns: (1) normal, (2) no g rowth or low plating efficiency, (3) low colony and high cluster numbe r, and (4) normal or high colony number with a large number of cluster s. The former two (1 and 2) can be referred to as nonleukemic patterns and latter two (3 and 4) as leukemic. In a search for a role for cyto kines in leukemic-type growth of MDS progenitor cells, marrow CD34(+) cells were purified up to 94% for 8 normal individuals and 88% for 12 MDS patients, using monoclonal antibodies and immunomagnetic microsphe res (MDS CD34(+) cells). The purified CD34(+) cells were cultured for 14 days with various combinations of cytokines, including recombinant human macrophage colony-stimulating factor (rM-CSF), granulocyte-CSF ( rG-CSF), granulocyte-macrophage-CSF (rGM-CSF), interleukin-3 (rIL-3), and stem cell factor (SCF; a ligand for c-kit) in serum-free medium. T he clonal growth of MDS CD34(+) cells supported by a combination of al l of the above cytokines was subdivided into the two patterns of leuke mic or nonleukemic, and then the role of individual or combined cytoki nes in proliferation and differentiation of MDS CD34(+) cells was anal yzed in each group. Evidence we obtained showed that SCF plays a centr al role in the leukemic-type growth of MDS CD34(+) cells and that G-CS F, GM-CSF, and/or IL-3 synergize with SCF to increase undifferentiated blast cell colonies and clusters over that seen in normal CD34(+) cel ls. SCF is present in either normal or MDS plasma at a level of nanogr ams per milliliter, and this physiologic concentration of SCF can stim ulate progenitor cells. This means that progenitor cells are continuou sly exposed to stimulation by SCF in vivo and that MDS leukemic cells have a growth advantage over normal blast cells. This depends, at leas t in part, on cytokines such as G-CSF, GM-CSF, IL-3, and SCF. (C) 1996 by The American Society of Hematology.