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Haematologica. 2005 Jan;90(1):54-9.

Differences in anti-apoptotic and multidrug resistance phenotypes in elderly and young acute myeloid leukemia patients are related to the maturation of blast cells.

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1
Department of Hematology, Hospital Universitario, Salamanca, Spain.

Abstract

BACKGROUND AND OBJECTIVES:

Elderly patients with acute myeloid leukemia (AML) have a less favorable outcome, which has been related, among other factors, to multidrug resistance (MDR) phenotypes.

DESIGN AND METHODS:

Freshly obtained erythrocyte-lysed bone marrow samples from 150 elderly patients (> 65 years) with de novo AML and 30 younger AML patients were analyzed using a 4-color immunofluorescence technique for quantitative expression of proteins associated with apoptosis (bcl-2, bax, APO2.7) and MDR (P-gp, MRP, LRP) in 3 blast cell subpopulations, defined according to their maturation stage.

RESULTS:

Although a homogeneous CD34+ blast cell population was more frequent in the elderly patients, (25% vs 7%, p=0.02), no statistically significant differences were detected between the two age groups in the expression of either apoptosis- or MDR-associated proteins, except for slightly higher quantities of LRP protein in the more immature CD34+ blast cell subset in the elderly AML cases (p=0.04). Interestingly, when different blast cell populations were compared, immature (CD34+) blast cells were characterized by higher levels of bcl-2 in both age groups and lower levels of APO2.7 in the elderly group. In addition, higher P-gp levels were found in CD34+ blast cells than in CD34-- ones in elderly AML patients. Reactivity for LRP was low in both elderly and younger patients.

INTERPRETATION AND CONCLUSIONS:

In summary, our results suggest that the higher resistance to chemotherapy observed in elderly AML patients could be related to a higher incidence of cases with a CD34+ homogeneous blast cell population, since these blast cells frequently display a more pronounced anti-apoptotic and MDR1 phenotype.

PMID:
15642669
[Indexed for MEDLINE]
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