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The Prognostic Effect of IKZF1 Deletions in ETV6::RUNX1 and High Hyperdiploid Childhood Acute Lymphoblastic Leukemia

Lookup NU author(s): Dr Amir EnshaeiORCiD, Professor Anthony MoormanORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2023 Wolters Kluwer Health. All rights reserved.IKZF1 deletions are an established prognostic factor in childhood acute lymphoblastic leukemia (ALL). However, their relevance in patients with good risk genetics, namely ETV6::RUNX1 and high hyperdiploid (HeH), ALL remains unclear. We assessed the prognostic impact of IKZF1 deletions in 939 ETV6::RUNX1 and 968 HeH ALL patients by evaluating data from 16 trials from 9 study groups. Only 3% of ETV6::RUNX1 cases (n = 26) were IKZF1-deleted; this adversely affected survival combining all trials (5-year event-free survival [EFS], 79% versus 92%; P = 0.02). No relapses occurred among the 14 patients with an IKZF1 deletion treated on a minimal residual disease (MRD)-guided protocols. Nine percent of HeH cases (n = 85) had an IKZF1 deletion; this adversely affected survival in all trials (5-year EFS, 76% versus 89%; P = 0.006) and in MRD-guided protocols (73% versus 88%; P = 0.004). HeH cases with an IKZF1 deletion had significantly higher end of induction MRD values (P = 0.03). Multivariate Cox regression showed that IKZF1 deletions negatively affected survival independent of sex, age, and white blood cell count at diagnosis in HeH ALL (hazard ratio of relapse rate [95% confidence interval]: 2.48 [1.32-4.66]). There was no evidence to suggest that IKZF1 deletions affected outcome in the small number of ETV6::RUNX1 cases in MRD-guided protocols but that they are related to higher MRD values, higher relapse, and lower survival rates in HeH ALL. Future trials are needed to study whether stratifying by MRD is adequate for HeH patients or additional risk stratification is necessary.

Publication metadata

Author(s): Ostergaard A, Enshaei A, Pieters R, Vora A, Horstmann MA, Escherich G, Johansson B, Heyman M, Schmiegelow K, Hoogerbrugge PM, Den Boer ML, Kuiper RP, Moorman AV, Boer JM, Van Leeuwen FN

Publication type: Article

Publication status: Published

Journal: HemaSphere

Year: 2023

Volume: 7

Issue: 5

Print publication date: 01/05/2023

Acceptance date: 09/03/2023

Date deposited: 02/06/2023

ISSN (electronic): 2572-9241

Publisher: Wolters Kluwer Health


DOI: 10.1097/HS9.0000000000000875


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Funder referenceFunder name
Blood Cancer UK
Oncode Institute
Princess Máxima Center Foundation, Talent Programme