Journal article
Enhancer retargeting of CDX2 and UBTF::ATXN7L3 define a subtype of high-risk B-progenitor acute lymphoblastic leukemia
S Kimura, L Montefiori, I Iacobucci, Y Zhao, Q Gao, EM Paietta, C Haferlach, AD Laird, PE Mead, Z Gu, W Stock, M Litzow, JM Rowe, SM Luger, SP Hunger, GL Ryland, B Schmidt, PG Ekert, A Oshlack, SM Grimmond Show all
Blood | AMER SOC HEMATOLOGY | Published : 2022
Abstract
Transcriptome sequencing has identified multiple subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL) of prognostic significance, but a minority of cases lack a known genetic driver. Here, we used integrated whole-genome (WGS) and -transcriptome sequencing (RNA-seq), enhancer mapping, and chromatin topology analysis to identify previously unrecognized genomic drivers in B-ALL. Newly diagnosed (n = 3221) and relapsed (n = 177) B-ALL cases with tumor RNA-seq were studied. WGS was performed to detect mutations, structural variants, and copy number alterations. Integrated analysis of histone 3 lysine 27 acetylation and chromatin looping was performed using HiChIP. We identified a subset..
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Awarded by Snowdome Foundation
Funding Acknowledgements
The authors thank the Haematology Tissue Bank (Peter MacCallum Cancer Centre/Royal Melbourne Hospital) and Children's Cancer Centre Tissue Bank (Murdoch Children's Research Institute) for assistance with sample collection and the Genomics Core Facility and Genomics Platform Group (University of Melbourne Centre for Cancer Research) for sequencing and analysis support. The authors are supported by the American and Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital; the St. Jude Children's Research Hospital Chromatin Collaborative (C.G. M.); National Institutes of Health National Cancer Institute (NCI) grants P30 CA021765, R35 CA197695 (C.G.M.), U10 CA180820 ( ECOG-ACRIN), UG1 CA232760 (M. L.), and UG1 CA189859 (E.M.P.); the Henry Schueler 41&9 Foundation (C.G.M.); a St. Baldrick's Foundation Robert J. Arceci Innovation Award (to C.G.M.); a Garwood Postdoctoral Fellowship of the Hematological Malignancies Program of the St Jude Children's Research Hospital Comprehensive Cancer Center (to S.K.); grants from the Wilson Centre for Blood Cancer Genomics (P.B.); the Snowdome Foundation (P.B.); the Peter MacCallum Cancer Foundation (G.L.R.); a SCOR Grant (7015-18); the Lymphoma and Leukemia Society (P.G. E.); the Perpetual Trustees and the Samuel Nissen Foundation (P.G. E.); and the National Health and Medical Research Council of Australia (A.O., GNT1140626).