Transcriptome analysis of primary adult B-cell lineage acute lymphoblastic leukemia identifies pathogenic variants and gene fusions, and predicts subtypes for in depth molecular diagnosis

B-cell acute lymphoblastic leukemia (B-ALL) is classified into subgroups based on known driver oncogenes and molecular lesions, including translocations and recurrent mutations. However, the current diagnostic tests do not identify subtypes or oncogenic lesions for all B-ALL samples, creating a hete...

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Bibliographic Details
Published in:European journal of haematology 2024-05, Vol.112 (5), p.731-742
Main Authors: Podgorica, Mirjam, Drivet, Elsa, Viken, Jonas Krag, Richman, Alyssa, Vestbøstad, Johanne, Szodoray, Peter, Kvam, Ann Kristin, Wik, Hilde Skuterud, Tjønnfjord, Geir E, Munthe, Ludvig A, Frietze, Seth, Schjerven, Hilde
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Cell lineage
Lesions
Leukemia
Lymphatic leukemia
Mutation
Precision medicine
Ribonucleic acid
RNA
Transcriptomes
Transcriptomics
Translocation
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Summary:B-cell acute lymphoblastic leukemia (B-ALL) is classified into subgroups based on known driver oncogenes and molecular lesions, including translocations and recurrent mutations. However, the current diagnostic tests do not identify subtypes or oncogenic lesions for all B-ALL samples, creating a heterogeneous B-ALL group of unknown subtypes. We sorted primary adult B-ALL cells and performed transcriptome analysis by bulk RNA sequencing (RNA-seq). Transcriptomic analysis of an adult B-ALL cohort allowed the classification of four patient samples with subtypes that were not previously revealed by standard gene panels. The leukemia of two patients were of the DUX4 subtype and two were CRLF2 Ph-like B-ALL. Furthermore, single nucleotide variant analysis detected the oncogenic NRAS-G12D, KRAS-G12D, and KRAS-G13D mutations in three of the patient samples, presenting targetable mutations. Additional oncogenic variants and gene fusions were uncovered, as well as multiple variants in the PDE4DIP gene across five of the patient samples. We demonstrate that RNA-seq is an effective tool for precision medicine in B-ALL by providing comprehensive molecular profiling of leukemia cells, identifying subtype and oncogenic lesions, and stratifying patients for appropriate therapy.
ISSN:0902-4441
1600-0609
DOI:10.1111/ejh.14164