Absence of caveolin-1 leads to delayed development of chronic lymphocytic leukemia in E mu-TCL1 mouse model

作者：Shukla Ashima; Cutucache Christine E; Sutton Garrett L; Pitner Michael A; Rai Karan; Rai Siddharth; Opavsky Rene; Swanson Patrick C; Joshi Shantaram S^*

来源：Experimental Hematology, 2016, 44(1): 30-37.

DOI：10.1016/j.exphem.2015.09.005

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United States. The tissue microenvironment, specifically the lymph nodes, influences the biological and clinical behavior of CLL cells. Gene expression profiling of CLL cells from peripheral blood, bone marrow, and lymph nodes revealed Cav-1 as one of the genes that might be involved in the pathogenesis of CLL. We have previously reported that the knockdown of Cav-1 in primary CLL cells exhibits a significant decrease in cell migration and immune synapse formation. However, the precise role of Cav-1 in CLL initiation and progression in vivo is not known. Therefore, we decreased the expression of Cav-1 in vivo by breeding E mu-TCL1 with cav-1 knockout mice. We observed a significant decrease in the number of CLL cells and rate of proliferation of CLL cells in spleen, liver, and bone marrow from E mu-TCL1-Cav1(-/+) and E mu-TCL1-Cav1(-/-) mice as compared with E mu-TCL1 mice. In addition, there was a significant increase in survival of E mu-TCL1-Cav1(-/+) and E mu-TCL1-Cav1(-/-) compared with E mu-TCL1 mice. Mechanistically, we observed a decrease in MAPK-Erk signaling measured by p-Erk levels in E mu-TCL1-Cav1(-/+) mice when compared with E mu-TCL1-Cav(wt/wt). Together these results indicate that decreased Cav-1 in E mu-TCL1 mice significantly delays the onset of CLL and decreases leukemic progression by inhibiting MAPK-Erk signaling, suggesting a role for Cav-1 in the proliferation and progression of CLL.

• 出版日期2016-1