期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 183, 期 4, 页码 588-600出版社
WILEY
DOI: 10.1111/bjh.15578
关键词
conditional knock-out mouse model; FLT3; haematopoiesis; lymphoid progenitors; lymphoid development
类别
资金
- Swedish Childhood Cancer Foundation [PR20130043, PR 20150063, PDS13/005, TFJ08]
- Gunnar Nilsson Foundation [522]
- ALF Clinical Research Award from Lund University Hospital [ALFSKANE 274081]
- Hemato-Linne
- Stem Therapy Program
- Swedish Research Council
- Swedish Research Council, Marie Sklodowska Curie Actions [2015-00135, 600398]
- UK MRC [G0801073, MC_UU_12009/5]
- MRC [MC_UU_00016/5, G0701761, G0801073, MC_UU_12009/7, G0900892, MC_UU_00016/7, G0501838, MC_UU_12009/5] Funding Source: UKRI
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.
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