Direct role of FLT3 in regulation of early lymphoid progenitors

Research output: Contribution to journalArticle

Abstract

Given that FLT3 expression is highly restricted on lymphoid progenitors, it is possible that the established role of FLT3 in the regulation of B and T lymphopoiesis reflects its high expression and role in regulation of lymphoid-primed multipotent progenitors (LMPPs) or common lymphoid progenitors (CLPs). We generated a Flt3 conditional knock-out (Flt3fl/fl) mouse model to address the direct role of FLT3 in regulation of lymphoid-restricted progenitors, subsequent to turning on Rag1 expression, as well as potentially ontogeny-specific roles in B and T lymphopoiesis. Our studies establish a prominent and direct role of FLT3, independently of the established role of FLT3 in regulation of LMPPs and CLPs, in regulation of fetal as well as adult early B cell progenitors, and the early thymic progenitors (ETPs) in adult mice but not in the fetus. Our findings highlight the potential benefit of targeting poor prognosis acute B-cell progenitor leukaemia and ETP leukaemia with recurrent FLT3 mutations using clinical FLT3 inhibitors.

Details

Authors
Organisations
External organisations
  • University of Oxford
  • John Radcliffe Hospital
  • Karolinska University Hospital
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology

Keywords

  • conditional knock-out mouse model, FLT3, haematopoiesis, lymphoid development, lymphoid progenitors
Original languageEnglish
Pages (from-to)588-600
JournalBritish Journal of Haematology
Volume183
Issue number4
Early online date2018 Sep 14
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes