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Non-canonical BRAF variants and rearrangements in hairy cell leukemia

STEPHEN E. LANGABEER*
Cancer Molecular Diagnostics, St. James’s Hospital, Dublin, D08 W9RT, Ireland
* Corresponding Author: STEPHEN E. LANGABEER. Email: email

Oncology Research https://doi.org/10.32604/or.2024.051218

Received 29 February 2024; Accepted 15 May 2024; Published online 07 June 2024

Abstract

Hairy cell leukemia (HCL) is an uncommon mature B-cell malignancy characterized by a typical morphology, immunophenotype, and clinical profile. The vast majority of HCL patients harbor the canonical BRAF V600E mutation which has become a rationalized target of the subsequently deregulated RAS-RAF-MEK-MAPK signaling pathway in HCL patients who have relapsed or who are refractory to front-line therapy. However, several HCL patients with a classical phenotype display non-canonical BRAF mutations or rearrangements. These include sequence variants within alternative exons and an oncogenic fusion with the IGH gene. Care must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BRAF V600E to include investigation of these uncommon mechanisms. Identification, functional characterization, and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required.

Keywords

Hairy cell leukemia; BRAF; Molecular diagnostics; Targeted therapy

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