@article{e6dff0245e294041831935fb416f8ca4,
title = "Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia",
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.",
author = "Roberts, {Kathryn G.} and Morin, {Ryan D.} and Jinghui Zhang and Martin Hirst and Yongjun Zhao and Xiaoping Su and Chen, {Shann Ching} and Debbie Payne-Turner and Churchman, {Michelle L.} and Harvey, {Richard C.} and Xiang Chen and Corynn Kasap and Chunhua Yan and Jared Becksfort and Finney, {Richard P.} and Teachey, {David T.} and Maude, {Shannon L.} and Kane Tse and Richard Moore and Steven Jones and Karen Mungall and Inanc Birol and Edmonson, {Michael N.} and Ying Hu and Buetow, {Kenneth E.} and Chen, {I. Ming} and Carroll, {William L.} and Lei Wei and Jing Ma and Maria Kleppe and Levine, {Ross L.} and Guillermo Garcia-Manero and Eric Larsen and Shah, {Neil P.} and Meenakshi Devidas and Gregory Reaman and Malcolm Smith and Paugh, {Steven W.} and Evans, {William E.} and Grupp, {Stephan A.} and Sima Jeha and Pui, {Ching Hon} and Gerhard, {Daniela S.} and Downing, {James R.} and Willman, {Cheryl L.} and Mignon Loh and Hunger, {Stephen P.} and Marra, {Marco A.} and Mullighan, {Charles G.}",
note = "Funding Information: We thank M. Tomasson and J. Cools for providing the MSCV- ETV6-PDGFRB -IRES-GFP and MSCV- NUP214-ABL1 -IRES-GFP constructs, respectively; D. Pei and C. Cheng for statistical analyses of cell line proliferation data; Garry Nolan for providing the Phoenix cell line ( http://www.stanford.edu/group/nolan/retroviral_systems/phx.html ); Beckman Coulter Genomics for Sanger Sequencing; and the Flow Cytometry Core Facility, Tissue Resources Core Facility, and Clinical Application of Core Technology (Affymetrix) Laboratory of the Hartwell Center for Bioinformatics and Biotechnology of St. Jude Children{\textquoteright}s Research Hospital. The correlative biology studies described in this manuscript were funded by grants from the National Institutes of Health (NIH) and philanthropic funds of the Children{\textquoteright}s Oncology Group and not a commercial entity. The sequencing was part-funded with Federal funds from the NCI and NIH under Contract No. N01-C0-12400 as part of the Therapeutically Applicable Research to Generate Effective Treatments initiative. This work was supported by funds provided as a supplement to the Children{\textquoteright}s Oncology Group Chair{\textquoteright}s award (CA098543, G.R.); grants to the COG, including U10 CA98543 (COG Chair{\textquoteright}s grant), U10 CA98413 (COG Statistical Center), and U24 CA114766 (COG Specimen Banking); a National Cancer Institute Strategic Partnering to Evaluate Cancer Signatures Program award CA114762 (W.L.C., I-M.C., R.C.H., and C.L.W.); NIH Cancer Center Core Grant CA21765 (J.R.D., C.G.M., W.E.E., C.-H.P., and S.J.); St. Jude Children{\textquoteright}s Research Hospital - Washington University Pediatric Cancer Genome Project; a Stand Up To Cancer Innovative Research Grant (C.G.M.); and the American Lebanese Syrian Associated Charities of St. Jude Children{\textquoteright}s Research Hospital. K.G.R. is supported by a National Health and Medical Research Council (Australia) Overseas Training Fellowship and a Haematology Society of Australia and New Zealand Novartis New Investigator Scholarship. R.D.M. is a Vanier Scholar (CIHR) and holds a MSFHR senior graduate studentship. M.A.M. is a UBC Canada Research Chair in Genome Science and a Michael Smith Senior Research Scholar. S.P.H. is the Ergen Family Chair in Pediatric Cancer. C.G.M. is a Pew Scholar in the Biomedical Sciences and a St. Baldrick{\textquoteright}s Scholar. S.P.H. is a member of the Bristol Myers Squibb pediatric dasatinib advisory board. ",
year = "2012",
month = aug,
day = "14",
doi = "10.1016/j.ccr.2012.06.005",
language = "English (US)",
volume = "22",
pages = "153--166",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}