ERG and c-MYC regulate a critical gene network in BCR::ABL1-driven B cell acute lymphoblastic leukemia

K Behrens; N Brajanovski; Z Xu; EM Viney; L DiRago; S Hediyeh-Zadeh; MJ Davis; RB Pearson; E Sanij; WS Alexander; AP Ng

Journal article

ERG and c-MYC regulate a critical gene network in BCR::ABL1-driven B cell acute lymphoblastic leukemia

K Behrens, N Brajanovski, Z Xu, EM Viney, L DiRago, S Hediyeh-Zadeh, MJ Davis, RB Pearson, E Sanij, WS Alexander, AP Ng

Science Advances | American Association for the Advancement of Science | Published : 2024

DOI: 10.1126/sciadv.adj8803

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Abstract

Philadelphia chromosome–positive B cell acute lymphoblastic leukemia (B-ALL), characterized by the BCR::ABL1 fusion gene, remains a poor prognosis cancer needing new therapeutic approaches. Transcriptomic profiling identified up-regulation of oncogenic transcription factors ERG and c-MYC in BCR::ABL1 B-ALL with ERG and c-MYC required for BCR::ABL1 B-ALL in murine and human models. Profiling of ERG- and c-MYC–dependent gene expression and analysis of ChIP-seq data established ERG and c-MYC coordinate a regulatory network in BCR::ABL1 B-ALL that controls expression of genes involved in several biological processes. Prominent was control of ribosome biogenesis, including expression of RNA polym..

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University of Melbourne Researchers

Kira Behrens Author

Zhen Xu Author

Richard Pearson Author

Elaine Sanij Author

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Awarded by Leukaemia Foundation

Funding Acknowledgements

This work was supported by fellowship (341020624) to K.B. from the Deutsche Forschungsgemeinschaft; fellowship (1058344), program (1113577), and investigator (1173342) grants to W.S.A. from the Australian National Health and Medical Research Council (NHMRC); project grants (1053792 and 1162052) and fellowship (1058586) to R.B.P. from NHMRC; Grants-in-Aid to A.P.N. and R.B.P. from the Cancer Council of Victoria, National Stem Cell Foundation of Australia Metcalf Prize for Stem Cell Research, and Alessandra's Fight Against Leukaemia (GoFundMe); the Leukaemia Foundation Breakthrough Fellowship to A.P.N.; the NHMRC Independent Research Institutes Infrastructure Support Scheme; the Australian Cancer Research Fund; and Victorian State Government Operational Infrastructure Support. E.S. is supported by a Victorian Cancer Agency Mid-Career Research Fellowship (MCRF19007).