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Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia

Leongamornlert, Daniel; Gutiérrez-Abril, Jesús; Lee, Soo Wah; Barretta, Emilio; Creasey, Tom; Gundem, Gunes; Levine, Max Fine; ... Papaemmanuil, Elli; + view all (2023) Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia. Blood Advances 10.1182/bloodadvances.2022008992. (In press). Green open access

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Abstract

Genomic profiling at diagnosis of B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL) in adults is used to guide disease classification, risk stratification and treatment decisions. Patients for which diagnostic screening fails to identify disease defining or risk stratifying lesions are classified as B-other ALL. We screened a cohort of 652 BCP-ALL cases enrolled in UKALL14 to identify and perform whole genome sequencing (WGS) on paired tumor-normal samples. For 52 B-other patients we compared WGS findings to data from clinical and research cytogenetics. WGS identifies a cancer associated event in 51/52 cases, this includes an established subtype defining genetic alteration in 5/52 that were previously missed by standard-of-care genetics. Of the 47 true B-other ALL we identified a recurrent driver in 87% (41). Complex karyotype by cytogenetics emerges as a heterogeneous group, including distinct genetic alterations associated with either favorable (DUX4-r) or poor outcomes (MEF2D-r, IGK::BCL2). For a subset of 31 cases, we integrate findings from RNA-sequencing (RNA-seq) analysis to include fusion gene detection, and classification by gene expression. Compared to RNA-seq, WGS was sufficient to detect and resolve recurrent genetic subtypes, however RNA-seq can provide orthogonal validation of findings. In conclusion, we demonstrate that WGS can identify clinically relevant genetic abnormalities missed by standard-of-care testing and identify leukemia driver events in virtually all cases of B-other ALL.

Type: Article
Title: Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/bloodadvances.2022008992
Publisher version: https://doi.org/10.1182/bloodadvances.2022008992
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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/10166175
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