BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma

被引：110

作者：

Correia, Cristina ^{[1
]}

Schneider, Paula A. ^{[1
]}

Dai, Haiming ^{[1
]}

Dogan, Ahmet ^{[2
]}

Maurer, Matthew J. ^{[3
]}

Church, Amy K. ^{[4
]}

Novak, Anne J. ^{[4
]}

Feldman, Andrew L. ^{[2
]}

Wu, Xiaosheng ^{[5
]}

Ding, Husheng ^{[1
]}

Meng, X. Wei ^{[1
]}

Cerhan, James R. ^{[6
]}

Slager, Susan L. ^{[3
]}

Macon, William R. ^{[2
]}

Habermann, Thomas M. ^{[4
]}

Karp, Judith E. ^{[7
]}

Gore, Steven D. ^{[7
]}

Kay, Neil E. ^{[4
]}

Jelinek, Diane F. ^{[4
,5
]}

Witzig, Thomas E. ^{[4
]}

Nowakowski, Grzegorz S. ^{[4
]}

Kaufmann, Scott H. ^{[1
,4
]}

机构：

[1] Mayo Clin, Div Oncol Res, Dept Oncol, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Lab Med & Pathol, Dept Oncol, Rochester, MN 55905 USA

[3] Mayo Clin, Div Biomed Stat & Bioinformat, Dept Hlth Sci Res, Rochester, MN 55905 USA

[4] Mayo Clin, Div Hematol, Dept Med, Rochester, MN 55905 USA

[5] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA

[6] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN 55905 USA

[7] Sidney Kimmel Canc Ctr Johns Hopkins, Div Hematol Malignancies, Baltimore, MD USA

来源：

BLOOD | 2015年 / 125卷 / 04期

基金：

美国国家卫生研究院;

关键词：

NON-HODGKINS-LYMPHOMAS; B-CELL LYMPHOMA; ABERRANT SOMATIC HYPERMUTATION; C-MYC; HISTOLOGICAL TRANSFORMATION; MALIGNANT-LYMPHOMA; PROGNOSTIC-FACTORS; PROGRESSION; MANAGEMENT; FAMILY;

D O I：

10.1182/blood-2014-04-571786

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Follicular lymphoma (FL), an indolent neoplasm caused by a t(14;18) chromosomal translocation that juxtaposes the BCL2 gene and immunoglobulin locus, has a variable clinical course and frequently undergoes transformation to an aggressive lymphoma. Although BCL2 mutations have been previously described, their relationship to FL progression remains unclear. In this study, we evaluated the frequency and nature of BCL2 mutations in 2 independent cohorts of grade 1 and 2 FLs, along with the correlation between BCL2 mutations, transformation risk, and survival. The prevalence of BCL2 coding sequence mutations was 12% in FL at diagnosis and 53% at transformation (P<.0001). The presence of these BCL2 mutations at diagnosis correlated with an increased risk of transformation (hazard ratio 3.6; 95% CI, 2.0-6.2; P<.0001) and increased risk of death due to lymphoma (median survival of 9.5 years with BCL2 mutations vs 20.4 years without; P = .012). In a multivariate analysis, BCL2 mutations and high FL international prognostic index were independent risk factors for transformation and death due to lymphoma. Some mutant Bcl-2 proteins exhibited enhanced antiapoptotic capacity in vitro. Accordingly, BCL2 mutations can affect antiapoptotic Bcl-2 function, are associated with increased activation induced cytidine deaminase expression, and correlate with increased risk of transformation and death due to lymphoma.

引用

页码：658 / 667

页数：10

共 62 条

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