The DLEU2/miR-15a/16-1 Cluster Controls B Cell Proliferation and Its Deletion Leads to Chronic Lymphocytic Leukemia

被引：620

作者：

Klein, Ulf ^{[1
,2
]}

Lia, Marie ^{[1
,2
]}

Crespo, Marta ^{[1
,2
]}

Siegel, Rachael ^{[1
,2
]}

Shen, Qiong ^{[1
,2
]}

Mo, Tongwei ^{[1
,2
]}

Ambesi-Impiombato, Alberto ^{[3
]}

Califano, Andrea ^{[1
,2
,3
]}

Migliazza, Anna ^{[1
,2
,6
]}

Bhagat, Govind ^{[1
,2
,4
]}

Dalla-Favera, Riccardo ^{[1
,2
,4
,5
]}

机构：

[1] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA

[2] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

[3] Columbia Univ, Joint Ctr Syst Biol, New York, NY 10032 USA

[4] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA

[5] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

[6] Nerviano Med Sci, I-20014 Milan, Italy

来源：

CANCER CELL | 2010年 / 17卷 / 01期

关键词：

TUMOR-SUPPRESSOR GENES; LYMPHOID MALIGNANCIES; MULTIPLE-MYELOMA; CHROMOSOME; 13Q14; DOWN-REGULATION; MANTLE CELL; BAND; ANTIGEN; CANCER; CLL;

D O I：

10.1016/j.ccr.2009.11.019

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Chronic lymphocytic leukemia (CLL) is a malignancy of B cells of unknown etiology. Deletions of the chromosomal region 13q14 are commonly associated with CLL, with monoclonal B cell lymphocytosis (MBL), which occasionally precedes CLL, and with aggressive lymphoma, suggesting that this region contains a tumor-suppressor gene. Here, we demonstrate that deletion in mice of the 13q14-minimal deleted region (MDR), which encodes the DLEU2/miR-15a/16-1 cluster, causes development of indolent B cell-autonomous, clonal lymphoproliferative disorders, recapitulating the spectrum of CLL-associated phenotypes observed in humans. miR-15a/16-1-deletion accelerates the proliferation of both human and mouse B cells by modulating the expression of genes controlling cell-cycle progression. These results define the role of 13q14 deletions in the pathogenesis of CLL.

引用

页码：28 / 40

页数：13

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