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Cyclin D2 overexpression drives B1a-derived MCL-like lymphoma in mice.

Abstract：

:Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with poor long-term overall survival. Currently, MCL research and development of potential cures is hampered by the lack of good in vivo models. MCL is characterized by recurrent translocations of CCND1 or CCND2, resulting in overexpression of the cell cycle regulators cyclin D1 or D2, respectively. Here, we show, for the first time, that hematopoiesis-specific activation of cyclin D2 is sufficient to drive murine MCL-like lymphoma development. Furthermore, we demonstrate that cyclin D2 overexpression can synergize with loss of p53 to form aggressive and transplantable MCL-like lymphomas. Strikingly, cyclin D2-driven lymphomas display transcriptional, immunophenotypic, and functional similarities with B1a B cells. These MCL-like lymphomas have B1a-specific B cell receptors (BCRs), show elevated BCR and NF-κB pathway activation, and display increased MALT1 protease activity. Finally, we provide preclinical evidence that inhibition of MALT1 protease activity, which is essential for the development of early life-derived B1a cells, can be an effective therapeutic strategy to treat MCL.

journal_name

J Exp Med

journal_title

The Journal of experimental medicine

authors

Pieters T,T'Sas S,Vanhee S,Almeida A,Driege Y,Roels J,Van Loocke W,Daneels W,Baens M,Marchand A,Van Trimpont M,Matthijssens F,Morscio J,Lemeire K,Lintermans B,Reunes L,Chaltin P,Offner F,Van Dorpe J,Hochepied T,Be

doi

10.1084/jem.20202280

subject

Has Abstract

pub_date

2021-10-04 00:00:00

issue

10

eissn

0022-1007

issn

1540-9538

pii

212576

journal_volume

218

pub_type

杂志文章

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