Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.

Cancer cell ·第 22 卷 ·第 2 期 ·2012-10-25

Roberts Kathryn G, Morin Ryan D, Zhang Jinghui, Hirst Martin, Zhao Yongjun, Su Xiaoping, Chen Shann-Ching, Payne-Turner Debbie, Churchman Michelle L, Harvey Richard C, Chen Xiang, Kasap Corynn, Yan Chunhua, Becksfort Jared, Finney Richard P, Teachey David T, Maude Shannon L, Tse Kane, Moore Richard, Jones Steven, Mungall Karen, Birol Inanc, Edmonson Michael N, Hu Ying, Buetow Kenneth E, Chen I-Ming, Carroll William L, Wei Lei, Ma Jing, Kleppe Maria, Levine Ross L, Garcia-Manero Guillermo, Larsen Eric, Shah Neil P, Devidas Meenakshi, Reaman Gregory, Smith Malcolm, Paugh Steven W, Evans William E, Grupp Stephan A, Jeha Sima, Pui Ching-Hon, Gerhard Daniela S, Downing James R, Willman Cheryl L, Loh Mignon, Hunger Stephen P, Marra Marco A, Mullighan Charles G

摘要

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.

文献信息

期刊

Cancer cell

期刊简称

Cancer Cell

ISSN

1535-6108

发表日期

2012-10-25

收录日期

2012-08-17

更新日期

2016-12-06

语言

英语

国家/地区

United States

NLM ID

101130617

外部链接

PubMed 原文查看期刊详情

分析服务

Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.

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