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Direct role of FLT3 in regulation of early lymphoid progenitors

Zriwil, Alya LU ; Böiers, Charlotta LU ; Kristiansen, Trine A. LU ; Wittmann, Lilian LU ; Yuan, Joan LU orcid ; Nerlov, Claus LU ; Sitnicka, Ewa LU and Jacobsen, Sten E.W. LU (2018) In British Journal of Haematology 183(4). p.588-600
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 (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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
conditional knock-out mouse model, FLT3, haematopoiesis, lymphoid development, lymphoid progenitors
in
British Journal of Haematology
volume
183
issue
4
pages
13 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85053465008
  • pmid:30596405
ISSN
0007-1048
DOI
10.1111/bjh.15578
language
English
LU publication?
yes
id
40491f2b-de08-4186-9dd8-89db65d964dc
date added to LUP
2018-10-23 12:37:08
date last changed
2024-11-27 15:11:04
@article{40491f2b-de08-4186-9dd8-89db65d964dc,
  abstract     = {{<p>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<sup>fl/fl</sup>) 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.</p>}},
  author       = {{Zriwil, Alya and Böiers, Charlotta and Kristiansen, Trine A. and Wittmann, Lilian and Yuan, Joan and Nerlov, Claus and Sitnicka, Ewa and Jacobsen, Sten E.W.}},
  issn         = {{0007-1048}},
  keywords     = {{conditional knock-out mouse model; FLT3; haematopoiesis; lymphoid development; lymphoid progenitors}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{4}},
  pages        = {{588--600}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{British Journal of Haematology}},
  title        = {{Direct role of FLT3 in regulation of early lymphoid progenitors}},
  url          = {{http://dx.doi.org/10.1111/bjh.15578}},
  doi          = {{10.1111/bjh.15578}},
  volume       = {{183}},
  year         = {{2018}},
}