Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation
Cette étude présente et évalue un nouveau test génétique, basé sur une détection de la mutation V600E du gène BRAF, pour le diagnostic d'une leucémie à tricholeucocytes
Hairy cell leukemia (HCL) is a distinct clinico-pathological entity that responds well to purine analogs but is sometimes difficult to differentiate from HCL-like disorders (e.g., splenic marginal zone lymphoma and HCL-variant). We recently identified the BRAF-V600E mutation as the disease-defining genetic event in HCL. Hereby, we describe a new, simple and inexpensive test for a genetics-based diagnosis of HCL in whole-blood samples, that detects BRAF-V600E through a sensitive allele-specific polymerase-chain-reaction qualitative assay followed by agarose-gel electrophoresis. This approach detected BRAF-V600E in all 117 leukemic HCL samples investigated containing as few as 0.1% leukemic cells. BRAF-V600E was detected at different time points during the disease course, even post-therapy, pointing to its pivotal role in HCL pathogenesis and maintenance of the leukemic clone. Conversely, 112 non-HCL chronic B-cell neoplasms, including 76 HCL-like disorders, were invariably negative for BRAF-V600E. This molecular assay is a powerful tool for improving the diagnostic accuracy in HCL.
Blood , résumé, 2011