Increased immature hematopoietic progenitor cells CD34+/CD38dim in myelodysplasia.
BACKGROUND
Myelodysplastic syndromes (MDS) are clonal disorders affecting hematopoietic progenitor cells (HPC). Despite the relevance of clonal CD34+ cells in developing MDS, only few studies analyze the phenotype of this cell population. The aim of this study was to evaluate phenotypic changes on HPC in MDS that could reflect abnormalities in the differentiation process of stem cells.


METHODS
We analyzed the expression of CD38 and HLA-DR on CD34+ cells by flow cytometry in 36 patients with MDS, as well as in healthy donors (n = 12) and patients with other hematological disorders: non-Hodgkin lymphomas and multiple myeloma, both in complete remission (CR) (n = 32); acute lymphoblastic leukemia in CR (n = 17); de novo acute myeloblastic leukemia (AML) at diagnosis (n = 22) and in CR (n = 37); and AML secondary to MDS at diagnosis (n = 19). Cases with available karyotype were grouped according to the International Prognostic Scoring System (IPSS).


RESULTS
Compared to normal BM, the fraction of immature HPC, characterized as CD34+bright, intermediate FSC/SSC, and CD38dim, was significantly increased in high risk MDS and secondary AML, but not in low risk MDS, (P < or = 0.001, P = 0.03, and P = 0.7). De novo AML showed decreased immature HPC. High numbers of immature HPC correlated with higher IPSS risk groups (P = 0.05) and showed significant impact on disease progression (P = 0.03).


CONCLUSIONS
Our study confirms that evaluation of CD38 expression pattern on HPC is an easy and reproducible test that allows evaluating the immature subset of progenitor cells. Increased immature HPC in high risk MDS and secondary AML may reflect blocked differentiation of CD34+ cells in these diseases.
Monreal
Mariela B
MB
FUNDALEU (Foundation to Fight Leukemia) and Centro de Investigacion Clinica A. Ocampo, Buenos Aires, Argentina. citometria@fundaleu.org.ar
Pardo
Maria L
ML
Pavlovsky
Miguel A
MA
Fernandez
Isolda
I
Corrado
Claudia S
CS
Giere
Isabel
I
Sapia
Sandra
S
Pavlovsky
Santiago
S
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D002454:Cell Differentiation; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000276:immunology; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000276:immunology*; D015588:Observer Variation; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000276:immunology; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors
D018952:Antigens, CD34; D006684:HLA-DR Antigens; D051997:ADP-ribosyl Cyclase 1