1. Direct role of<scp>FLT</scp>3 in regulation of early lymphoid progenitors
- Author
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Trine A. Kristiansen, Sten Eirik W. Jacobsen, Claus Nerlov, Joan Yuan, Alya Zriwil, Charlotta Böiers, Ewa Sitnicka, and Lilian Wittmann
- Subjects
0301 basic medicine ,medicine.medical_specialty ,lymphoid development ,Bone Marrow Cells ,Thymus Gland ,Biology ,Recombination-activating gene ,Mice ,03 medical and health sciences ,fluids and secretions ,0302 clinical medicine ,lymphoid progenitors ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Animals ,Lymphopoiesis ,Progenitor cell ,FLT3 ,B cell ,Progenitor ,Homeodomain Proteins ,Mice, Knockout ,Fetus ,Hematology ,Haematological Malignancy ,Cell Differentiation ,hemic and immune systems ,haematopoiesis ,Lymphoid Progenitor Cells ,conditional knock‐out mouse model ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,fms-Like Tyrosine Kinase 3 ,030220 oncology & carcinogenesis ,embryonic structures ,Cancer research ,Research Paper - Abstract
Summary 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.
- Published
- 2018