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IKZF1 alterations are not associated with outcome in 498 adults with B-precursor ALL enrolled in the UKALL14 trial

Lookup NU author(s): Emilio Barretta, Dr Tobias Menne, Professor Anthony MoormanORCiD

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Abstract

© 2021 by The American Society of HematologyIKZF1 deletions (DIKZF1) are commonly detected in B-precursor acute lymphoblastic leukemia (ALL; B-ALL) and are widely assumed to have a significant impact on outcome. We compared the ability of multiplex ligand-dependent probe amplification (MLPA) and polymerase chain reaction (PCR) to detect DIKZF1 and to determine the impact on event-free survival of patients with precursor B-ALL aged 23 to 65 years recruited to the completed trial UKALL14 (ISRCTN 66541317). From 655 recruits with BCR-ABL11 and BCRABL12 B-ALL, all available diagnostic DNA samples (76% of the recruited population) were screened by multiplex end point PCR covering 4 deletions: dominant-negative (DN) D4-7 or the loss of function D2-7, D4-8, and D2-8 (n 5 498), MLPA (n 5 436), or by both (n 5 420). Although patients with BCR-ABL12 DIKZF1 were more likely to have minimal residual disease at the end of induction, we did not find any impact of DIKZF1 (including subgroup analysis for DN or loss-of-function lesions) or the IKZF1plus genotype on event-free, overall survival, or relapse risk by univariable or multivariable analyses. Consistent with the technical approach, MLPA not only detected a wider range of deletions than PCR but also failed to detect some PCR-detected lesions. The main difference between our study and others reporting an association between DIKZF1 and outcome is the older age of participants in our population. The impact of DIKZF1 in ALL may be less marked in an older population of patients. Our study underscores the need for analyses in large, harmonized data sets. This trial was registered at www.clinicaltrials.gov as #NCT01085617.

Publication metadata

Author(s): Mitchell RJ, Kirkwood AA, Barretta E, Clifton-Hadley L, Lawrie E, Lee S, Leongamornlert D, Marks DI, McMillan AK, Menne TF, Papaemmanuil E, Patel B, Patrick P, Rowntree CJ, Zareian N, Alapi KZ, Moorman AV, Fielding AK

Publication type: Article

Publication status: Published

Journal: Blood Advances

Year: 2021

Volume: 5

Issue: 17

Pages: 3322-3332

Print publication date: 14/09/2021

Online publication date: 03/09/2021

Acceptance date: 03/05/2021

ISSN (print): 2473-9529

ISSN (electronic): 2473-9537

Publisher: American Society of Hematology

URL: https://doi.org/10.1182/BLOODADVANCES.2021004430

DOI: 10.1182/BLOODADVANCES.2021004430

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