Epigenetic features support the diagnosis of B-cell prolymphocytic leukemia and identify two clinico-biological subtypes
Résumé
The recognition of B-cell prolymphocytic leukemia (B-PLL) as a separate entity is controversial based on the current classification systems. Here, we analyze the DNA methylome of a cohort of 20 B-PLL cases diagnosed according to the ICC/WHO-HAEM4R guidelines, and compare them with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and normal B cell subpopulations. Unsupervised principal component analyses suggest that B-PLL is epigenetically distinct from CLL, MCL and SMZL, which is further supported by robust differential methylation signatures in B-PLL. We also observe that B-PLL can be segregated into two epitypes with differential clinico-biological characteristics. B-PLL epitype 1 carries lower IGHV somatic hypermutation and a less profound germinal center-related DNA methylation imprint than epitype 2. Furthermore, epitype 1 is significantly enriched in mutations affecting MYC and SF3B1, and displays DNA hypomethylation and gene upregulation signatures enriched in MYC targets. Despite the low sample size, patients from epitype 1 have an inferior overall survival than those of epitype 2. This study provides relevant insights into the biology and differential diagnosis of B-PLL, and potentially identifies two subgroups with distinct biological and clinical features.
Domaines
Sciences du Vivant [q-bio]| Origine | Publication financée par une institution |
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