Differences in anti-apoptotic and multidrug resistance phenotypes in elderly and young acute myeloid leukemia patients are related to the maturation of blast cells.
OBJECTIVE
Elderly patients with acute myeloid leukemia (AML) have a less favorable outcome, which has been related, among other factors, to multidrug resistance (MDR) phenotypes.


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.


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.
Suárez
Lilia
L
Department of Hematology, Hospital Universitario, Salamanca, Spain.
Vidriales
María Belén
MB
Moreno
María-José
MJ
López
Antonio
A
García-Laraña
José
J
Pérez-López
Cristina
C
Tormo
Mar
M
Lavilla
Esperanza
E
López-Berges
María Consuelo
MC
de Santiago
María
M
San Miguel
Jesús F
JF
Orfao
Alberto
A
D000208:Acute Disease; D000328:Adult; D000367:Age Factors; D000368:Aged; D018952:Antigens, CD34; D017209:Apoptosis / Q000187:drug effects*; D001752:Blast Crisis / Q000473:pathology*; D018432:Drug Resistance, Multiple; D005260:Female; D019450:Genes, MDR / Q000235:genetics / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged
D018952:Antigens, CD34