SYK Is a Critical Regulator of FLT3 in Acute Myeloid Leukemia.
Puissant, Alexandre ; Fenouille, Nina ; Alexe, Gabriela ; Pikman, Yana ; Bassil, Christopher F ; Mehta, Swapnil ; Du, Jinyan ; Kazi, Julhash U. LU
; Luciano, Frédéric
and Rönnstrand, Lars
LU
, et al.
(2014)
In Cancer Cell
25(2).
p.226-242
- Abstract
- Cooperative dependencies between mutant oncoproteins and wild-type proteins are critical in cancer pathogenesis and therapy resistance. Although spleen tyrosine kinase (SYK) has been implicated in hematologic malignancies, it is rarely mutated. We used kinase activity profiling to identify collaborators of SYK in acute myeloid leukemia (AML) and determined that FMS-like tyrosine kinase 3 (FLT3) is transactivated by SYK via direct binding. Highly activated SYK is predominantly found in FLT3-ITD positive AML and cooperates with FLT3-ITD to activate MYC transcriptional programs. FLT3-ITD AML cells are more vulnerable to SYK suppression than FLT3 wild-type counterparts. In a FLT3-ITD in vivo model, SYK is indispensable for myeloproliferative... (More)
- Cooperative dependencies between mutant oncoproteins and wild-type proteins are critical in cancer pathogenesis and therapy resistance. Although spleen tyrosine kinase (SYK) has been implicated in hematologic malignancies, it is rarely mutated. We used kinase activity profiling to identify collaborators of SYK in acute myeloid leukemia (AML) and determined that FMS-like tyrosine kinase 3 (FLT3) is transactivated by SYK via direct binding. Highly activated SYK is predominantly found in FLT3-ITD positive AML and cooperates with FLT3-ITD to activate MYC transcriptional programs. FLT3-ITD AML cells are more vulnerable to SYK suppression than FLT3 wild-type counterparts. In a FLT3-ITD in vivo model, SYK is indispensable for myeloproliferative disease (MPD) development, and SYK overexpression promotes overt transformation to AML and resistance to FLT3-ITD-targeted therapy. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4334651
- author
- Puissant, Alexandre
; Fenouille, Nina
; Alexe, Gabriela
; Pikman, Yana
; Bassil, Christopher F
; Mehta, Swapnil
; Du, Jinyan
; Kazi, Julhash U.
LU
; Luciano, Frédéric
and Rönnstrand, Lars
LU
, et al. (More)
- Puissant, Alexandre
; Fenouille, Nina
; Alexe, Gabriela
; Pikman, Yana
; Bassil, Christopher F
; Mehta, Swapnil
; Du, Jinyan
; Kazi, Julhash U.
LU
; Luciano, Frédéric
; Rönnstrand, Lars
LU
; Kung, Andrew L
; Aster, Jon C
; Galinsky, Ilene
; Stone, Richard M
; Deangelo, Daniel J
; Hemann, Michael T
and Stegmaier, Kimberly
(Less)
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer Cell
- volume
- 25
- issue
- 2
- pages
- 226 - 242
- publisher
- Cell Press
- external identifiers
-
- pmid:24525236
- wos:000331498000010
- scopus:84893550362
- ISSN
- 1878-3686
- DOI
- 10.1016/j.ccr.2014.01.022
- language
- English
- LU publication?
- yes
- id
- d2a9228e-fd42-4648-9609-df00a2e9fdd7 (old id 4334651)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24525236?dopt=Abstract
- date added to LUP
- 2016-04-01 10:46:19
- date last changed
- 2022-03-19 23:46:59
@article{d2a9228e-fd42-4648-9609-df00a2e9fdd7,
abstract = {{Cooperative dependencies between mutant oncoproteins and wild-type proteins are critical in cancer pathogenesis and therapy resistance. Although spleen tyrosine kinase (SYK) has been implicated in hematologic malignancies, it is rarely mutated. We used kinase activity profiling to identify collaborators of SYK in acute myeloid leukemia (AML) and determined that FMS-like tyrosine kinase 3 (FLT3) is transactivated by SYK via direct binding. Highly activated SYK is predominantly found in FLT3-ITD positive AML and cooperates with FLT3-ITD to activate MYC transcriptional programs. FLT3-ITD AML cells are more vulnerable to SYK suppression than FLT3 wild-type counterparts. In a FLT3-ITD in vivo model, SYK is indispensable for myeloproliferative disease (MPD) development, and SYK overexpression promotes overt transformation to AML and resistance to FLT3-ITD-targeted therapy.}},
author = {{Puissant, Alexandre and Fenouille, Nina and Alexe, Gabriela and Pikman, Yana and Bassil, Christopher F and Mehta, Swapnil and Du, Jinyan and Kazi, Julhash U. and Luciano, Frédéric and Rönnstrand, Lars and Kung, Andrew L and Aster, Jon C and Galinsky, Ilene and Stone, Richard M and Deangelo, Daniel J and Hemann, Michael T and Stegmaier, Kimberly}},
issn = {{1878-3686}},
language = {{eng}},
number = {{2}},
pages = {{226--242}},
publisher = {{Cell Press}},
series = {{Cancer Cell}},
title = {{SYK Is a Critical Regulator of FLT3 in Acute Myeloid Leukemia.}},
url = {{http://dx.doi.org/10.1016/j.ccr.2014.01.022}},
doi = {{10.1016/j.ccr.2014.01.022}},
volume = {{25}},
year = {{2014}},
}