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Lookup NU author(s): Professor Anthony MoormanORCiD, Emilio Barretta, Ellie Butler, Eleanor Ward, Dr Amir EnshaeiORCiD, Claire Schwab, Dr Tom Creasey, Dr Daniel Leongamornlert, Dr Tobias Menne
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021, The Author(s). Chromosomal abnormalities are established prognostic markers in adult ALL. We assessed the prognostic impact of established chromosomal abnormalities and key copy number alterations (CNA) among 652 patients with B-cell precursor ALL treated on a modern MRD driven protocol. Patients with KMT2A-AFF1, complex karyotype (CK) and low hypodiploidy/near-triploidy (HoTr) had high relapse rates 50%, 60% & 53% and correspondingly poor survival. Patients with BCR-ABL1 had an outcome similar to other patients. JAK-STAT abnormalities (CRLF2, JAK2) occurred in 6% patients and were associated with a high relapse rate (56%). Patients with ABL-class fusions were rare (1%). A small group of patients with ZNF384 fusions (n = 12) had very good survival. CNA affecting IKZF1, CDKN2A/B, PAX5, BTG1, ETV6, EBF1, RB1 and PAR1 were assessed in 436 patients. None of the individual deletions or profiles were associated with survival, either in the cohort overall or within key subgroups. Collectively these data indicate that primary genetic abnormalities are stronger prognostic markers than secondary deletions. We propose a revised UKALL genetic risk classification based on key established chromosomal abnormalities: (1) very high risk: CK, HoTr or JAK-STAT abnormalities; (2) high risk: KMT2A fusions; (3) Tyrosine kinase activating: BCR-ABL1 and ABL-class fusions; (4) standard risk: all other patients.
Author(s): Moorman AV, Barretta E, Butler ER, Ward EJ, Twentyman K, Kirkwood AA, Enshaei A, Schwab C, Creasey T, Leongamornlert D, Papaemmanuil E, Patrick P, Clifton-Hadley L, Patel B, Menne T, McMillan AK, Harrison CJ, Rowntree CJ, Marks DI, Fielding AK
Publication type: Article
Publication status: Published
Journal: Leukemia
Year: 2022
Volume: 36
Pages: 625-636
Print publication date: 01/03/2022
Online publication date: 16/10/2021
Acceptance date: 30/09/2021
Date deposited: 19/05/2022
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41375-021-01448-2
DOI: 10.1038/s41375-021-01448-2
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