Next Generation Sequencing In Patients With Hairy Cell Leukemia (Hcl)

Hairy cell leukemia (HCL) is a rare mature B-cell chronic lymphoproliferative disorder, characterized by the identification of the BRAF(V600E) mutation. In the variant form (HCL-v), the BRAF(V600E) mutation is absent, but mutations of the MAP2K1 gene are observed in a third of the cases. These mutations lead to a constitutive activation of the MAP-kinase pathway. The development of high-throughput sequencing techniques makes it possible to better define the mutational landscape of HCL and HCL-v. In HCL, recurrent mutations of CDKN1B (13%) and KLF2 (9.5%) are often identified and associated with BRAF(V600E). CDKN18 codes for the p27 protein involved in cell cycle regulation and KFL2 for a negative regulator of the NF-kappa B pathway. In HCL-v, the mutations most frequently identified are MAPZKI (42%), TP53 (26.5%), U2AF1 (16%) and KDM6A (16%) mutations. U2AF1 encodes a spliceosome component and KDM6A, for a lysine demethylase. In HCL and HCL-v, many mutations involve genes involved in epigenetic regulation, including KMT2C (MLL3), KDM6A (UTX), ARID1A, AR1D18, CREBBP, and EZH2. The identification of the mutations profile in the hairy cells proliferative disorders makes it possible to adapt a personalized treatment, particularly in the refractory forms of HCL or HCL-v.