Laboratoire d’hématologie, CaenFrance
Hairy cell leukaemia (HCL) is a rare mature B-cell chronic lymphoproliferative disorder, characterised by the identification of BRAFV600E mutation. In the variant form (HCL-v), the BRAFV600E mutation is absent, but mutations of the MAP2K1 gene are observed in a third of cases. These mutations lead to 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 BRAFV600E. CDKN1B encodes p27 which is involved in cell cycle regulation and KFL2 encodes for a negative regulator of the NF-kB pathway. In HCL-v, the mutations most frequently identified are MAP2K1 (42%), TP53 (26.5%), U2AF1 (16%) and KDM6A (16%) mutations. U2AF1 encodes for a spliceosome component and KDM6A encodes a lysine demethylase. In HCL and HCL-v, many mutations involve genes implicated in epigenetic regulation, including KMT2C (MLL3), KDM6A (UTX), ARID1A, ARID1B, CREBBP, and EZH2. Identifying the mutation profile in hairy cell proliferative disorders will enable development of personalised treatment, particularly for refractory forms of HCL or HCL-v.