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Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study

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

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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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Funding

Funder referenceFunder name
A21019
15036Bloodwise (Formerly Leukaemia and Lymphoma Research) Closed Competition
C27995/A9609

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