1. Direct role of FLT3 in regulation of early lymphoid progenitors.
- Author
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Zriwil A, Böiers C, Kristiansen TA, Wittmann L, Yuan J, Nerlov C, Sitnicka E, and Jacobsen SEW
- Subjects
- Animals, Bone Marrow Cells pathology, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Lymphoid Progenitor Cells pathology, Mice, Mice, Knockout, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Thymus Gland metabolism, Thymus Gland pathology, fms-Like Tyrosine Kinase 3 genetics, Bone Marrow Cells metabolism, Cell Differentiation, Lymphoid Progenitor Cells metabolism, Lymphopoiesis, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, fms-Like Tyrosine Kinase 3 metabolism
- 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 (Flt3
fl/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., (© 2018 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2018
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