Author/Authors :
Klein، نويسنده , , Ulf and Lia، نويسنده , , Marie and Crespo، نويسنده , , Marta and Siegel، نويسنده , , Rachael and Shen، نويسنده , , Qiong and Mo، نويسنده , , Tongwei and Ambesi-Impiombato، نويسنده , , Alberto and Califano، نويسنده , , Andrea and Migliazza، نويسنده , , Anna and Bhagat، نويسنده , , Govind and Dalla-Favera، نويسنده , , Riccardo، نويسنده ,
Abstract :
Summary
c 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.
