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Lookup NU author(s): Dr Tom Creasey, Emilio Barretta, Dr Sarra Ryan, Ellie Butler, Dr Daniel Leongamornlert, Dr Tobias Menne, Professor Anthony MoormanORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Despite being predominantly a childhood disease, the incidence of ALL has a second peak in adults aged 60 years and over. These older adults fare extremely poorly with existing treatment strategies and very few studies have undertaken a comprehensive genetic and genomic characterisation to improve prognosis in this age group. We performed cytogenetic, single nucleotide polymorphism (SNP) array and next generation sequencing (NGS) analyses on samples from 210 patients aged ≥60 years from the UKALL14 and UKALL60+ clinical trials. BCR-ABL1 positive disease was present in 26% (55/210) of patients, followed by low hypodiploidy/near triploidy in 13% (28/210). Cytogenetically cryptic rearrangements in CRLF2, ZNF384 and MEF2D were detected in 5%, 1% and 1% of patients respectively. Copy number abnormalities were common and deletions in ALL driver genes were seen in 77% of cases. IKZF1 deletion was present in 51% (40/78) of samples tested and the IKZF1plus profile identified in over a third (28/77) of BCP-ALL cases. The genetic good risk abnormalities high hyperdiploidy (n=2), ETV6-RUNX1 (no cases) and ERG deletion (no cases) were exceptionally rare in this cohort. RAS pathway mutations were seen in 17% (4/23) of screened samples. KDM6A abnormalities, including biallelic deletions, were discovered in 5% (4/78) of SNP array and 9% (2/23) of NGS samples, and represent a novel, potentially therapeutically actionable lesions using EZH2 inhibitors. Outcome remained poor with five-year event-free (EFS) and overall survival (OS) rates of 17% and 24% respectively across the cohort indicating a need for novel therapeutic strategies.
Author(s): Creasey T, Barretta E, Ryan SL, Butler E, Kirkwood AA, Leongamornlert D, Papaemmanuil E, Patrick P, Clifton-Hadley L, Patel B, Menne T, McMillan AK, Harrison CJ, Rowntree CJ, Morley N, Marks DI, Fielding AK, Moorman AV
Publication type: Article
Publication status: Published
Journal: Haematologica
Year: 2022
Volume: 107
Issue: 9
Pages: 2051-2063
Print publication date: 01/09/2022
Online publication date: 18/11/2021
Acceptance date: 09/09/2021
Date deposited: 02/08/2023
ISSN (print): 0390-6078
ISSN (electronic): 1592-8721
Publisher: Ferrata Storti Foundation
URL: https://doi.org/10.3324/haematol.2021.279177
DOI: 10.3324/haematol.2021.279177
PubMed id: 34788984
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