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

Authors :
Daniel Leongamornlert
Jesús Gutiérrez-Abril
Soo Wah Lee
Emilio Barretta
Tom Creasey
Gunes Gundem
Max Fine Levine
Juan Esteban Arango Ossa
Konstantinos Liosis
Juan Santiago Medina-Martinez
Krisztina Zuborne Alapi
Amy A Kirkwood
Laura Clifton-Hadley
Pip Patrick
David Jones
Laura J O'Neill
Adam P Butler
Christine J Harrison
Peter J Campbell
Bela Patel
Anthony V Moorman
Adele K Fielding
Elli Papaemmanuil
Source :
Blood Advances.
Publication Year :
2023
Publisher :
American Society of Hematology, 2023.

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.

Subjects

Subjects :
Hematology

Details

ISSN :
24739537 and 24739529
Database :
OpenAIRE
Journal :
Blood Advances
Accession number :
edsair.doi...........6dc97e42f7836d4265bec8a9cef878fd
Full Text :
https://doi.org/10.1182/bloodadvances.2022008992