PROLIFERATION AND DIFFERENTIATION OF MYELODYSPLASTIC CD34(- PHENOTYPIC SUBPOPULATIONS OF MARROW CD34(+) CELLS() CELLS )

In a search for a mechanism to explain the impaired growth of progenit or cells in patients with myelodysplastic syndromes (MDS), marrow CD34 (+) cells were purified up to 94.9% +/- 4.2% for normal individuals an d 88.1% +/- 17.6% for MDS patients, using monoclonal antibodies and im muno-magnetic microspheres (MDS CD34(+) cells). Phenotypic subpopulati ons of these CD34(+) cells were analyzed for CD38, HLA-DR, CD33, CD13, CD14, CD41 and CD3 plus CD19, in association with proliferative and d ifferentiative capacities. The 15 studies performed included 12 MDS pa tients. Coexpression rate of CD13 significantly increased in the MDS C D34(+) cell population with a value of 91.4% +/- 11.6% and ranging fro m 60.3% to 100%, and exceeded 99% in four studies, whereas that of nor mal CD34(+) cells was 49.9% +/- 15.8%, ranging from 28.2% to 70.1% (P < .001). Coexpression rate of CD38, HLA-DR, CD33, CD14, and CD3 plus C D19 in MDS CD34(+) cells did not significantly differ from that of nor mal CD34(+) cells. The tota I number of colonies and clusters grown fr om 100 normal marrow CD34(+) cells was 40.4 +/- 8.6, the range being f rom 27.2 to 50.3; this varied in MDS marrow CD34(+) cells with a value of 34.0 +/- 28.7, the range being 0 to 95.9. The lineage of colonies and clusters promoted by MDS marrow CD34(+) cells was predominantly co mmitted to nonerythroid with impaired differentiation in 13 of 15 stud ies (87%). CD13 is first expressed during hematopoiesis by colony-form ing unit granulocyte-macrophage and is absent in erythroid progenitors . Therefore, this study provides direct evidence for the lineage commi tment of MDS CD34(+) cells to nonerythroid with impaired differentiati on and explains the mechanism of nil or low colony expression of MDS p rogenitor cells to erythroid lineage. (C) 1995 by The American Society of Hematology.