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

In a search for a mechanism to explain the impaired growth of progenitor cells in patients with myelodysplastic syndromes (MDS), marrow CD34(+) cells were purified up to 94.9% +/- 4.2% for normal individuals and 88.1% +/- 17.6% for MDS patients, using monoclonal antibodies and immuno-magnetic microspheres (MDS CD34(+) cells). Phenotypic subpopulations of these CD34(+) cells were analyzed for CD38, HLA-DR, CD33, CD13, CD14, CD41 and CD3 plus CD19, in association with proliferative and differentiative capacities. The 15 studies performed included 12 MDS patients. Coexpression rate of CD13 significantly increased in the MDS CD34(+) cell population with a value of 91.4% +/- 11.6% and ranging from 60.3% to 100%, and exceeded 99% in four studies, whereas that of normal 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 CD19 in MDS CD34(+) cells did not significantly differ from that of normal CD34(+) cells. The tota I number of colonies and clusters grown from 100 normal marrow CD34(+) cells was 40.4 +/- 8.6, the range being from 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 committed to nonerythroid with impaired differentiation in 13 of 15 studies (87%). CD13 is first expressed during hematopoiesis by colony-forming unit granulocyte-macrophage and is absent in erythroid progenitors. Therefore, this study provides direct evidence for the lineage commitment of MDS CD34(+) cells to nonerythroid with impaired differentiation and explains the mechanism of nil or low colony expression of MDS progenitor cells to erythroid lineage. (C) 1995 by The American Society of Hematology.