Project

B1 step ahead of mantle cell lymphoma (MCL)

Code
3G0A4822
Duration
01 January 2022 → 31 December 2025
Funding
Research Foundation - Flanders (FWO)
Promotor-spokesperson
Research disciplines
  • Medical and health sciences
    • Hematology
    • Cancer biology
    • Hematology
    • Transcription and translation
Keywords
transcriptional regulation mantle cell lymphoma SOX11 B1 lymphocytes
 
Project description

Although SOX11 is not expressed in normal lymphoid cells or their progenitors, high SOX11 levels is observed in mantle cell lymphoma (MCL). Previous functional studies on MCL cell lines pointed towards a pivotal oncogenic role for SOX11 in this disease, however the molecular mechanism of action is not known. We generated a conditional SOX11 overexpression mouse model. B-cell restricted gain of SOX11 in combination with loss of the tumor suppressor p53 resulted in fast spontaneous development of MCL, with 100% penetrance. As such we have developed a reliable and relevant MCL mouse model that we will use in this project to identify the downstream targets and drugable nodes within the oncogenic pathways. These data will allow us to propose novel targeted therapeutic strategies and evaluate their efficicay for the treatment of these aggressive lymphoma/leukemia subtypes. Our preliminary data demonstrated that SOX11 overexpression results in a pre-lymphoma increase of fetal-derived B1 B-cell population, suggesting that these may represent the cell of origin of the murine MCL development, and putatively also human MCL. We hypthesize that targeting B1-specific pathways while sparing conventional B2 lymphocytes may represent an interesting novel therapeutic strategy for MCL.