Epigenetic features support the diagnosis of B-cell prolymphocytic leukemia and identify two clinico-biological subtypes

ABSTRACT: 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 as well as gain 1q, 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279602 | GEO | 2025/01/08

REPOSITORIES: GEO