Affiliation:
1. QIMR Berghofer Medical Research Institute
2. University of Melbourne
3. University of Lausanne
4. Royal Brisbane and Women's Hospital
5. Monash University
Abstract
Abstract
Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in adults, characterized by the expansion of CD19+ CD5+ B cells. The origin of CLL remains debated, with one model suggesting that CLL cells carrying mutations in the variable regions of immunoglobulin are derived from post-germinal center B cells, whereas unmutated CLL cells originate from CD5+ mature B cell precursors. The cytokines BAFF and APRIL each play a significant role in CLL cell survival and accumulation, but their involvement in disease initiation is unclear. Using the TCL1-transgenic (Tg) model, we have demonstrated that BAFF, but not, APRIL is needed for the initiation and dissemination of CLL. In the absence of BAFF or its receptor BAFF-R, expression of the TCL1 transgene increases CLL cell numbers in the peritoneal cavity but does not allow dissemination into the periphery. BAFF binding to BAFF-R is not required for the survival of peritoneal CLL cells but for the expression of tumor-promoting genes, likely allowing peritoneal CLL cells to disseminate to other sites to drive CLL. Our findings unveil BAFF as an unrecognized tumor-promoting cytokine in CLL. Combining current CLL therapies with BAFF inhibition may offer dual benefits: reducing peripheral tumor burden and suppressing transformed CLL cell output.
Publisher
Research Square Platform LLC