Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia.
Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia.
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DOI：
10.1038/s41375-022-01590-5
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发表时间：
2022-06
期刊：
影响因子：
11.4
通讯作者：
Barata JT
中科院分区：
文献类型：
--
作者：
Oliveira ML;Veloso A;Garcia EG;Iyer S;Pereira C;Barreto VM;Langenau DM;Barata JT
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric cancer. Amongst the wide array of driver mutations, 10% of T-ALL patients display gain-of-function mutations in the IL-7 receptor α chain (IL-7Rα, encoded by IL7R), which occur in different molecular subtypes of this disease. However, it is still unclear whether IL-7R mutational activation is sufficient to transform T-cell precursors. Also, which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here, we demonstrate that mutant IL7R alone is capable of inducing T-ALL with long-latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally, we find that mutant IL7R collaborates with Myc to induce early onset T-ALL in transgenic zebrafish, supporting a model where these pathways collaborate to drive leukemogenesis. T-ALLs co-expressing mutant IL7R and Myc activate STAT5 and AKT pathways, harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T-ALLs expressing Myc alone. Moreover, limiting-dilution cell transplantation experiments reveal that activated IL-7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T-ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.
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影响因子：
50.3
作者：
Blackburn JS;Liu S;Wilder JL;Dobrinski KP;Lobbardi R;Moore FE;Martinez SA;Chen EY;Lee C;Langenau DM
通讯作者：
Langenau DM
影响因子：
20.3
作者：
Chiang, Mark Y.;Wang, Qing;Pear, Warren S.
通讯作者：
Pear, Warren S.
DOI：
10.1084/jem.20081922
发表时间：
2009-04-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
González-García S;García-Peydró M;Martín-Gayo E;Ballestar E;Esteller M;Bornstein R;de la Pompa JL;Ferrando AA;Toribio ML
通讯作者：
Toribio ML
影响因子：
11.4
作者：
Cramer, Sarah D.;Hixon, Julie A.;Durum, Scott K.
通讯作者：
Durum, Scott K.
影响因子：
11.4
作者：
Canté-Barrett K;Spijkers-Hagelstein JA;Buijs-Gladdines JG;Uitdehaag JC;Smits WK;van der Zwet J;Buijsman RC;Zaman GJ;Pieters R;Meijerink JP
通讯作者：
Meijerink JP