Direct role of FLT3 in regulation of early lymphoid progenitors

Summary Given that FLT 3 expression is highly restricted on lymphoid progenitors, it is possible that the established role of FLT 3 in the regulation of B and T lymphopoiesis reflects its high expression and role in regulation of lymphoid‐primed multipotent progenitors ( LMPP s) or common lymphoid progenitors ( CLP s). We generated a Flt3 conditional knock‐out ( Flt3 fl/fl ) mouse model to address the direct role of FLT 3 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 FLT 3, independently of the established role of FLT 3 in regulation of LMPP s and CLP s, in regulation of fetal as well as adult early B cell progenitors, and the early thymic progenitors ( ETP s) 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 FLT 3 mutations using clinical FLT 3 inhibitors.