title: Differences in anti-apoptotic and multidrug resistance phenotypes in elderly and young acute myeloid leukemia patients are related to the maturation of blast cells.
abstract: 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.
authors.affiliation: Department of Hematology, Hospital Universitario, Salamanca, Spain.
authors.forename: Lilia
authors.initials: L
authors.lastname: Suárez
authors.forename: María Belén
authors.initials: MB
authors.lastname: Vidriales
authors.forename: María-José
authors.initials: MJ
authors.lastname: Moreno
authors.forename: Antonio
authors.initials: A
authors.lastname: López
authors.forename: José
authors.initials: J
authors.lastname: García-Laraña
authors.forename: Cristina
authors.initials: C
authors.lastname: Pérez-López
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.forename: Esperanza
authors.initials: E
authors.lastname: Lavilla
authors.forename: María Consuelo
authors.initials: MC
authors.lastname: López-Berges
authors.forename: María
authors.initials: M
authors.lastname: de Santiago
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: 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
chemical_list: D018952:Antigens, CD34