Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.
Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.
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DOI：
10.1016/j.ccr.2012.06.005
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发表时间：
2012-08-14
期刊：
影响因子：
50.3
通讯作者：
Mullighan CG
中科院分区：
文献类型：
--
作者：
Roberts KG;Morin RD;Zhang J;Hirst M;Zhao Y;Su X;Chen SC;Payne-Turner D;Churchman ML;Harvey RC;Chen X;Kasap C;Yan C;Becksfort J;Finney RP;Teachey DT;Maude SL;Tse K;Moore R;Jones S;Mungall K;Birol I;Edmonson MN;Hu Y;Buetow KE;Chen IM;Carroll WL;Wei L;Ma J;Kleppe M;Levine RL;Garcia-Manero G;Larsen E;Shah NP;Devidas M;Reaman G;Smith M;Paugh SW;Evans WE;Grupp SA;Jeha S;Pui CH;Gerhard DS;Downing JR;Willman CL;Loh M;Hunger SP;Marra MA;Mullighan CG
基因组分析已经确定了一种具有IKZF 1改变的高危B祖细胞急性淋巴细胞白血病（B-ALL）亚型，其基因表达谱与BCR-ABL 1阳性ALL相似，结果较差（Ph样ALL）。在Ph样ALL中激活激酶信号的遗传改变知之甚少。我们对15例Ph样ALL患者进行了转录组和全基因组测序，鉴定了涉及ABL 1、JAK 2、PDGFRB、CRLF 2和EPOR的重排，IL 7 R和FLT 3的激活突变，以及编码JAK 2负调节因子LNK的SH 2B 3的缺失。重要的是，这些改变中的几种诱导转化，其被酪氨酸激酶抑制剂减弱，这表明这些患者的治疗结果可以通过靶向治疗来改善。
Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL, and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2 and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2 negative regulator LNK. Importantly, several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.
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影响因子：
51.1
作者：
Den Boer, Monique L.;van Slegtenhorst, Marjon;De Menezes, Renee X.;Cheok, Meyling H.;Buijs-Gladdines, Jessica G. C. A. M.;Peters, Susan T. C. J. M.;Van Zutven, Laura C. M.;Beverloo, H. Berna;Van der Spek, Peter J.;Escherich, Gaby;Horstmann, Martin A.;Janka-Schoub, Gritta E.;Kamps, Willem A.;Evans, William E.;Pieters, Rob
通讯作者：
Pieters, Rob
影响因子：
50.3
作者：
Armstrong, SA;Kung, AL;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
影响因子：
158.5
作者：
Apperley, JF;Gardembas, M;Goldman, JM
通讯作者：
Goldman, JM
影响因子：
3.2
作者：
Bowman, W. Paul;Larsen, Eric L.;Devidas, Meenakshi;Linda, Stephen B.;Blach, Laurie;Carroll, Andrew J.;Carroll, William L.;Pullen, D. Jeanette;Shuster, Jonathan;Willman, Cheryl L.;Winick, Naomi;Camitta, Bruce M.;Hunger, Stephen P.;Borowitz, Michael J.
通讯作者：
Borowitz, Michael J.
影响因子：
2.4
作者：
Cross, Nicholas C. P.;Reiter, Andreas
通讯作者：
Reiter, Andreas