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 immunomagnetic 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 total 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.
Sawada
K
K
Department of Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
Sato
N
N
Notoya
A
A
Tarumi
T
T
Hirayama
S
S
Takano
H
H
Koizumi
K
K
Yasukouchi
T
T
Yamaguchi
M
M
Koike
T
T
D000368:Aged; D000754:Anemia, Refractory, with Excess of Blasts / Q000473:pathology; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation; D002455:Cell Division; D002469:Cell Separation; D015672:Erythroid Precursor Cells / Q000473:pathology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000473:pathology*
D015703:Antigens, CD; D018952:Antigens, CD34