Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia
- 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.
DOIAbstract
SummaryGenomic 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 p...
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