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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.

Original publication

DOI

10.1111/bjh.15578

Type

Journal article

Journal

Br J Haematol

Publication Date

11/2018

Volume

183

Pages

588 - 600

Keywords

FLT3, conditional knock‐out mouse model, haematopoiesis, lymphoid development, lymphoid progenitors, Animals, Bone Marrow Cells, Cell Differentiation, Homeodomain Proteins, Lymphoid Progenitor Cells, Lymphopoiesis, Mice, Mice, Knockout, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Thymus Gland, fms-Like Tyrosine Kinase 3