Differences in anti-apoptotic and multidrug resistance phenotypes in elderly and young acute myeloid leukemia patients are related to the maturation of blast cells.
Haematologica
; 90(1): 54-9, 2005 Jan.
Article
in En
| MEDLINE
| ID: mdl-15642669
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 ANDMETHODS:
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 ANDCONCLUSIONS:
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blast Crisis
/
Leukemia, Myeloid
/
Apoptosis
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Haematologica
Year:
2005
Document type:
Article
Affiliation country: