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Chronic Lymphocytic Leukemia

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

Leukemia volume 22, pages 2184–2192 (2008)Cite this article

Abstract

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.

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Acknowledgements

We thank the patients for their participation, and the Hematology–Oncology nurses and physician assistants for their special contributions. The work was supported in part by the National Institutes of Health, the Leukemia and Lymphoma Society and the VA Research Service (JBW); Glenn/AFAR (RD); and GlaxoSmithKline and the Deane Laboratory (WJS).

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Authors and Affiliations

  1. Department of Medicine, Duke University and VA Medical Centers, Durham, NC, USA

    J B Weinberg, A D Volkheimer, N Jiang, Y Chen & K Bond

  2. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    M Mihovilovic, J O Moore, J P Gockerman, L F Diehl, C M de Castro, D A Rizzieri, M C Levesque, R DeKroon & W J Strittmatter

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  1. J B Weinberg
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Correspondence to J B Weinberg.

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Weinberg, J., Volkheimer, A., Mihovilovic, M. et al. Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia. Leukemia 22, 2184–2192 (2008). https://doi.org/10.1038/leu.2008.241

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