Evaluation of BRAF mutations in hairy cell leukemia and other B-cell malignancies

Introduction HCL (hairy cell leukemia) is an uncommon chronic lymphoproliferative disorder of the B-cell lymphocytes. Heterozygote mutation of BRAF V600E is one of the most important mutations that identified by whole-exom sequencing. The aim of this study was to investigate BRAF mutation in Iranian patients with HCL and other B-cell .Material and Methods:From August 2014 to April 2017 A total of 45 patients (30 patients with HCL-classic, 5 patients with HCL-variant and the rest of them (10 patients) withother class B Lymphoproliferative malignancy including, 6 marginal zone lymphomas and 4 lymphoplasmacytic lymphomas) who were referred to hematologyoncology and stem cell transplantation research center were recruited for our study. Mononuclear cells (MNCs) consisting hairy cells were separated from the bone marrow of HCL patients at the time of initial diagnosis, by density gradient centrifugation on Ficoll-Paque. Genomic DNAs were extracted using salting out procedure. We performed the mutation analysis by direct sequencingResult :Analysis was performed to detect BRAF(V600E) mutation in all patients. Of the 30 Classical HCL patients , 25 patients had BRAF mutation. None of the patients with HCLVariant and other lymphoproliferative malignancies had BRAF (V600E) mutation. Discussion: Detection of this mutation in Hairy cell leukemia can be helpful in diagnosis and discrimination of other B cell malignancy such as splenic marginal zone lymphoma (SMZL), undifferentiated spleniclymphoma/leukemia, chronic lymphoproliferative disordersDNA sequencing is the gold standard for mutation detection, however, it requires a mutant allele threshold of 10% . The use of additional and more sensitive techniques such as Allele-Specific Real-Time PCR Assays may increase the percent of Classical HCL patients with BRAF mutations .

Keywords:

BRAF , Seqyencing , HCL