Abstract

Background: BRAF V600E mutations were recently identified in the leukemic cells from patients with hairy cell leukemia (HCL) that this mutation in exon 15 is considered the disease-defining mutation in HCL. Objectives: This meta-analysis aimed to report the prevalence of BRAF V600E mutation in HCL patients. Methods: Three databases including PubMed, Scopus, and Web of Science up to 2017 were searched for the prevalence of BRAF mutation in HCL patients. A random effects meta-analysis was performed using the Comprehensive Meta-Analysis software version 2.0 with the event rate (ER) and 95% confidence interval (95% CI). Results: Out of 552 articles identified from the search, 11 were included included and were analyzed for meta-analysis study. The studies in meta-analysis included 437 patients with HCL, of which 353 (80.8%) patients had BRAF V600E mutation. The pooled ER of the studies was 81.5% (95% CI: 69.5%–89.5%). The Begg's test did not show publication bias, but the Egger's test showed publication bias. Conclusions: With regard to the mentioned limitations, the prevalence of BRAF mutation in HCL patients was >80%. In future studies, considering sex, age, and other variables can exactly show the correlation between these variables with the detection of BRAF mutation.

Introduction

Hairy cell leukemia (HCL) is a chronic B-cell lymphoid leukemia characterized by pancytopenia, splenomegaly, myelofibrosis, and the presence in peripheral blood, bone marrow, and spleen of atypical lymphoid cells with a hairy aspect.[1] There are approximately 1000 and 1600 new cases of HCL per year in the US and Europe, respectively. The prevalence of the disease is unknown, although HCL accounts for 2% of all types of leukemia, and the incidence of HCL increases annually.[2] Variant HCL (HCLv) is now included in the World Health Organization classification as a provisional entity and is no longer considered to be biologically related to classic HCL (HCLc). The clinical course of HCLv is variable, but usually more aggressive, and the median survival of patients with HCLv is significantly shorter than that of HCLc.[3] HCLc is a B-cell malignancy with distinctive immunophenotype, typically expressing CD20, CD22, CD25, CD11c, CD103, CD123, annexin A1, and tartrate-resistant acid phosphatase.[4] HCLc responds to purine nucleoside analogs, while HCLv cases are resistant and are more aggressive compared with the classic variant.[5] Clinically, HCL has an indolent course with splenomegaly, progressive cytopenias, low numbers of circulating leukemia cells, and no lymphadenopathy. BRAF V600E mutations were recently identified in the leukemic cells from patients with HCL.[6] This mutation in exon 15 is considered the disease-defining mutation in HCL, but single HCL cases lacking this mutation have been described.[7] It has demonstrated BRAF V600E-negative cases of HCL.[8] In some studies, BRAF V600E mutations were found in 100

| Figure. 1  Flowchart of the study

| Figure. 2  Forest plot of the prevalence of the studies included in the meta‑analysis (n = 11)

| Figure. 3  Funnel plot of the random effect of the studies for the prevalence of BRAF mutation in patients with hairy cell leukemia

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