| Literature DB >> 22897847 |
Kathryn G Roberts1, Ryan D Morin, Jinghui Zhang, Martin Hirst, Yongjun Zhao, Xiaoping Su, Shann-Ching Chen, Debbie Payne-Turner, Michelle L Churchman, Richard C Harvey, Xiang Chen, Corynn Kasap, Chunhua Yan, Jared Becksfort, Richard P Finney, David T Teachey, Shannon L Maude, Kane Tse, Richard Moore, Steven Jones, Karen Mungall, Inanc Birol, Michael N Edmonson, Ying Hu, Kenneth E Buetow, I-Ming Chen, William L Carroll, Lei Wei, Jing Ma, Maria Kleppe, Ross L Levine, Guillermo Garcia-Manero, Eric Larsen, Neil P Shah, Meenakshi Devidas, Gregory Reaman, Malcolm Smith, Steven W Paugh, William E Evans, Stephan A Grupp, Sima Jeha, Ching-Hon Pui, Daniela S Gerhard, James R Downing, Cheryl L Willman, Mignon Loh, Stephen P Hunger, Marco A Marra, Charles G Mullighan.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2012 PMID： 22897847 PMCID： PMC3422513 DOI： 10.1016/j.ccr.2012.06.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743