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Direct role of FLT 3 in regulation of early lymphoid progenitors
Author(s) -
Zriwil Alya,
Böiers Charlotta,
Kristiansen Trine A.,
Wittmann Lilian,
Yuan Joan,
Nerlov Claus,
Sitnicka Ewa,
Jacobsen Sten E. W.
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15578
Subject(s) - lymphopoiesis , progenitor cell , biology , progenitor , immunology , cancer research , stem cell , microbiology and biotechnology
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.