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DNA methylation subtypes of Waldenström’s macroglobulinemia identified

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Patients with Waldenström’s macroglobulinemia (WM) can be subclassified using patterns of DNA methylation to find differing molecular signatures among patients, according to a study published in Blood.

In this study, researchers integrated genome-wide DNA methylation, transcriptome, mutation and other phenotypic features of tumor cells from 35 patients with MYD88-mutated WM in relation to normal plasma and B cell subsets.

Patients naturally appeared to split into 2 groups according to DNA methylation patterns as a result of memory B cells (MBCs) and plasma cells (PCs).

Hypomethylation in the MBC subtypes was enriched in motifs belonging to PU.1, TCF3 and OCT2 transcription factors and involved elevated MYD88/TLR pathway activity whereas PC subtypes had marked global hypomethylation and selective overexpression of histone genes.

Those in the MBC subtype harbored significantly more clonal CXCR4 mutations, deletion 13q, splenomegaly, and thrombocytopenia. PC subtypes harbored more deletion 6q, gain 6p, and had increased frequencies of IGHV3 genes, CD38 surface expression, and plasmacytic differentiation features.

The authors concluded that their findings “illustrate a novel approach to subclassify WM patients using patterns of DNA methylation and reveal divergent molecular signatures among WM patients.


Roos-Weil D, Giacopelli B, Armand M, et al. Identification of two DNA methylation subtypes of Waldenström’s macroglobulinemia with plasma and memory B cell features [published online ahead of print, 2020 May 26]. Blood. 2020;blood.2020005081. doi:10.1182/blood.2020005081