CD34+ cells from acute myeloid leukemia, myelodysplastic syndromes, and normal bone marrow display different apoptosis and drug resistance-associated phenotypes.
Clin Cancer Res
; 10(22): 7599-606, 2004 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-15569991
ABSTRACT
Myelodysplastic syndromes and acute myeloid leukemia (AML) are heterogeneous disorders in which conflicting results in apoptosis and multidrug resistance (MDR) have been reported. We have evaluated by multiparameter flow cytometry the expression of apoptosis- (APO2.7, bcl-2, and bax) and MDR-related proteins [P-glycoprotein (P-gp), multidrug resistance protein (MRP), and lung resistance protein (LRP)] specifically on bone marrow (BM) CD34+ cells, and their major CD32-/dim and CD32+ subsets, in de novo AML (n=90), high-risk myelodysplastic syndrome (n=9), and low-risk myelodysplastic syndrome (n=21) patients at diagnosis, and compared with normal BM CD34+ cells (n=6). CD34+ myeloid cells from AML and high-risk myelodysplastic syndrome patients displayed higher expression of bcl-2 (P <0.0001) and lower reactivity for APO2.7 (P=0.002) compared with low-risk myelodysplastic syndrome and normal controls. Similar results applied to the two predefined CD34+ myeloid cell subsets. No significant differences were found in the expression of P-gp, MRP, and LRP between low-risk myelodysplastic syndrome patients and normal BM, but decreased expression of MRP (P <0.03) in AML and high-risk myelodysplastic syndromes and P-gp (P=0.008) in high-risk myelodysplastic syndromes were detected. Hierarchical clustering analysis showed that low-risk myelodysplastic syndrome patients were clustered next to normal BM samples, whereas high-risk myelodysplastic syndromes were clustered together and mixed with the de novo AML patients. In summary, increased resistance to chemotherapy of CD34+ cells from both AML and high-risk myelodysplastic syndromes would be explained more appropriately in terms of an increased antiapoptotic phenotype rather than a MDR phenotype. In low-risk myelodysplastic syndromes abnormally high apoptotic rates would be restricted to the CD34- cell compartments.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndromes Mielodisplásicas
/
Células da Medula Óssea
/
Leucemia Mieloide Aguda
/
Antígenos CD34
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article