학술논문
Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia
Document Type
article
Author
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
Source
Cancer Cell. 22(2)
Subject
Language
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.