Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia.
Leukemia
; 22(12): 2184-92, 2008 Dec.
Article
em En
| MEDLINE
| ID: mdl-18784741
Survival of chronic lymphocytic leukemia (CLL) cells requires sustained activation of the antiapoptotic PI-3-K/Akt pathway, and many therapies for CLL cause leukemia cell death by triggering apoptosis. Blood lipoprotein particles are either pro- or antiapoptotic. High-density lipoprotein particles are antiapoptotic through sphingosine-1-phosphate receptor 3-mediated activation of the PI-3-K/Akt pathway. Apolipoprotein E4 (apoE4)-very low density lipoproteins (VLDL) increase apoptosis, but the apoE2-VLDL and apoE3-VLDL isoforms do not. As increased B-cell apoptosis favors longer survival of CLL patients, we hypothesized that APOE4 genotype would beneficially influence the clinical course of CLL. We report here that women (but not men) with an APOE4 genotype had markedly longer survival than non-APOE4 patients. VLDL is metabolized to low-density lipoprotein through lipoprotein lipase. Higher levels of lipoprotein lipase mRNA in these CLL patients correlated with shorter survival. The beneficial effect of APOE4 in CLL survival is likely mediated through APOE4 allele-specific regulation of leukemia cell apoptosis. The APOE allele and genotype distribution in these CLL patients is the same as in unaffected control populations, suggesting that although APOE genotype influences CLL outcome and response to therapy, it does not alter susceptibility to developing this disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Linfocítica Crônica de Células B
/
Apolipoproteína E4
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Leukemia
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Reino Unido