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Genetic and genomic analysis of acute lymphoblastic leukaemia in older adults reveals a distinct profile of abnormalities: analysis of 210 patients from the UKALL14 and UKALL60+ clinical trials

Creasey, T; Barretta, E; Ryan, SL; Butler, E; Kirkwood, AA; Leongamornlert, D; Papaemmanuil, E; ... Moorman, AV; + view all (2021) Genetic and genomic analysis of acute lymphoblastic leukaemia in older adults reveals a distinct profile of abnormalities: analysis of 210 patients from the UKALL14 and UKALL60+ clinical trials. Haematologica 10.3324/haematol.2021.279177. (In press). Green open access

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Abstract

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.

Type: Article
Title: Genetic and genomic analysis of acute lymphoblastic leukaemia in older adults reveals a distinct profile of abnormalities: analysis of 210 patients from the UKALL14 and UKALL60+ clinical trials
Location: Italy
Open access status: An open access version is available from UCL Discovery
DOI: 10.3324/haematol.2021.279177
Publisher version: https://doi.org/10.3324/haematol.2021.279177
Language: English
Additional information: © 2021 Ferrata Storti Foundation. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10139451
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