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Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia.

Publication ,  Journal Article
Weinberg, JB; Volkheimer, AD; Mihovilovic, M; Jiang, N; Chen, Y; Bond, K; Moore, JO; Gockerman, JP; Diehl, LF; de Castro, CM; Rizzieri, DA ...
Published in: Leukemia
December 2008

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.

Duke Scholars

Published In

Leukemia

DOI

EISSN

1476-5551

Publication Date

December 2008

Volume

22

Issue

12

Start / End Page

2184 / 2192

Location

England

Related Subject Headings

  • Survival Analysis
  • Sex Distribution
  • Risk Factors
  • Male
  • Lipoprotein Lipase
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Immunology
  • Humans
  • Genotype
  • Genetic Predisposition to Disease
 

Citation

APA
Chicago
ICMJE
MLA
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Weinberg, J. B., Volkheimer, A. D., Mihovilovic, M., Jiang, N., Chen, Y., Bond, K., … Strittmatter, W. J. (2008). Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia. Leukemia, 22(12), 2184–2192. https://doi.org/10.1038/leu.2008.241
Weinberg, J. B., A. D. Volkheimer, M. Mihovilovic, N. Jiang, Y. Chen, K. Bond, J. O. Moore, et al. “Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia.Leukemia 22, no. 12 (December 2008): 2184–92. https://doi.org/10.1038/leu.2008.241.
Weinberg JB, Volkheimer AD, Mihovilovic M, Jiang N, Chen Y, Bond K, et al. Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia. Leukemia. 2008 Dec;22(12):2184–92.
Weinberg, J. B., et al. “Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia.Leukemia, vol. 22, no. 12, Dec. 2008, pp. 2184–92. Pubmed, doi:10.1038/leu.2008.241.
Weinberg JB, Volkheimer AD, Mihovilovic M, Jiang N, Chen Y, Bond K, Moore JO, Gockerman JP, Diehl LF, de Castro CM, Rizzieri DA, Levesque MC, Dekroon R, Strittmatter WJ. Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia. Leukemia. 2008 Dec;22(12):2184–2192.

Published In

Leukemia

DOI

EISSN

1476-5551

Publication Date

December 2008

Volume

22

Issue

12

Start / End Page

2184 / 2192

Location

England

Related Subject Headings

  • Survival Analysis
  • Sex Distribution
  • Risk Factors
  • Male
  • Lipoprotein Lipase
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Immunology
  • Humans
  • Genotype
  • Genetic Predisposition to Disease