| First Author | Shukla A | Year | 2016 |
| Journal | Exp Hematol | Volume | 44 |
| Issue | 1 | Pages | 30-7.e1 |
| PubMed ID | 26435347 | Mgi Jnum | J:316140 |
| Mgi Id | MGI:6834219 | Doi | 10.1016/j.exphem.2015.09.005 |
| Citation | Shukla A, et al. (2016) Absence of caveolin-1 leads to delayed development of chronic lymphocytic leukemia in Emu-TCL1 mouse model. Exp Hematol 44(1):30-7.e1 |
| abstractText | 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 Emu-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 Emu-TCL1-Cav1(-/+) and Emu-TCL1-Cav1(-/-) mice as compared with Emu-TCL1 mice. In addition, there was a significant increase in survival of Emu-TCL1-Cav1(-/+) and Emu-TCL1-Cav1(-/-) compared with Emu-TCL1 mice. Mechanistically, we observed a decrease in MAPK-Erk signaling measured by p-Erk levels in Emu-TCL1-Cav1(-/+) mice when compared with Emu-TCL1-Cav(wt/wt). Together these results indicate that decreased Cav-1 in Emu-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. |
