New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes.

Classical hairy cell leukemia (HCL-c) is a rare lymphoid neoplasm. mutation, detected in more than 80% of the cases, is described as a driver mutation, but additional genetic abnormalities appear to be necessary for the disease progression. For cases of HCL-c harboring a wild-type gene, the differential diagnosis of the variant form of HCL (HCL-v) or splenic diffuse red pulp lymphoma (SDRPL) is complex. We selected a panel of 21 relevant genes based on a literature review of whole exome sequencing studies (, , , , , , , , , , , , , , , , , , , , and ). We analyzed 20 HCL-c and 4 HCL-v patients. The analysis of diagnostic samples mutations in ( = 18), ( = 4), ( = 3), ( = 2), ( = 2), ( = 2), ( = 2) ( = 1) and ( = 1). was found in 90% (18/20) of HCL-c patients. In HCL-c patients with , other mutations were found in 33% (6/18) of cases. All 4 HCL-v patients had mutations in epigenetic regulatory genes: ( = 2), ( = 1) or ( = 1). The analysis of sequential samples (at diagnosis and relapse) from 5 patients (2 HCL-c and 3 HCL-v), showed the presence of 2 new subclonal mutations ( and ) in one patient and variations of the mutated allele frequency in 2 other cases. In the HCL-v disease, we described new mutations targeting that encode a lysine demethylase protein. This opens new perspectives for personalized medicine for this group of patients.