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

Ashima Shukla, Christine E Cutucache, Garrett L. Sutton, Michael A. Pitner, Karan Rai, Siddharth Rai, Rene Opavsky, Patrick C. Swanson, Shantaram S Joshi

Research output: Contribution to journalArticle

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Abstract

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 Eμ-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 Eμ-TCL1-Cav1-/+ and Eμ-TCL1-Cav1-/- mice as compared with Eμ-TCL1 mice. In addition, there was a significant increase in survival of Eμ-TCL1-Cav1-/+ and Eμ-TCL1-Cav1-/- compared with Eμ-TCL1 mice. Mechanistically, we observed a decrease in MAPK-Erk signaling measured by p-Erk levels in Eμ-TCL1-Cav1-/+ mice when compared with Eμ-TCL1-Cavwt/wt. Together these results indicate that decreased Cav-1 in Eμ-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.

Original languageEnglish (US)
Pages (from-to)30-37.e1
JournalExperimental Hematology
Volume44
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Caveolin 1
B-Cell Chronic Lymphocytic Leukemia
Lymph Nodes
Bone Marrow
Gene Expression Profiling
Knockout Mice
Synapses
Cell Movement
Breeding
Blood Cells
Leukemia
Spleen
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Hematology

Cite this

Absence of caveolin-1 leads to delayed development of chronic lymphocytic leukemia in Eμ-TCL1 mouse model. / Shukla, Ashima; Cutucache, Christine E; Sutton, Garrett L.; Pitner, Michael A.; Rai, Karan; Rai, Siddharth; Opavsky, Rene; Swanson, Patrick C.; Joshi, Shantaram S.

In: Experimental Hematology, Vol. 44, No. 1, 01.01.2016, p. 30-37.e1.

Research output: Contribution to journalArticle

Shukla, Ashima ; Cutucache, Christine E ; Sutton, Garrett L. ; Pitner, Michael A. ; Rai, Karan ; Rai, Siddharth ; Opavsky, Rene ; Swanson, Patrick C. ; Joshi, Shantaram S. / Absence of caveolin-1 leads to delayed development of chronic lymphocytic leukemia in Eμ-TCL1 mouse model. In: Experimental Hematology. 2016 ; Vol. 44, No. 1. pp. 30-37.e1.
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