Phenotypic and functional analysis of bone marrow progenitor cell compartment in bone marrow failure.
Many laboratory findings have demonstrated that the haemopoietic stem cell compartment is defective in aplastic anaemia (AA). AA bone marrow (BM) and peripheral blood (PB) are profoundly deficient in colony-forming cells, and AA progenitors fail to proliferate in long-term assays even in the presence of an intact stroma. Our study was designed to characterize some quantitative and qualitative aspects of the progenitor cell defect in AA. Using flow cytometric analysis of BM from new AA patients and from those recovering after immunosuppressive therapy, we determined that the numbers of CD34+ and CD33+ cells were markedly decreased in AA. Although PB neutrophil counts did not correlate with BM CD34+ cell numbers in acute disease, there was an association between the overall severity of the disease and the degree of CD34+ cell reduction. A decrease in BM CD33+ cells was a common finding in MDS patients, but reduction in CD34+ cells was found only in some hypoplastic MDS cases. Sorting experiments demonstrated lower plating efficiency for purified CD34+ cells from AA BM in comparison to controls. Thus, diminished colony formation of total BM appeared to result from both quantitative and qualitative defects. Based on the association between increased cycling and c-kit receptor expression on CD34+ cells, we found that the mitotically active CD34+ cells bearing the c-kit antigen were reduced in AA. With clinical improvement, CD34+ and CD33+ cells increased in correlation with PB parameters, but they did not return to normal values. Sorted CD34+ cells from recovered patents showed improved plating efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
Maciejewski
J P
JP
Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.
Anderson
S
S
Katevas
P
P
Young
N S
NS
D000328:Adult; D000741:Anemia, Aplastic / Q000473:pathology* / Q000628:therapy; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology*; D002453:Cell Cycle; D002469:Cell Separation / Q000379:methods; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D063268:Sialic Acid Binding Ig-like Lectin 3; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases