Blood: DNA methylation spectrum identifies two giant globulinemia (WM) subtypes

Epigenetic changes in B-cell differentiation have produced DNA methylation characteristics specific to the B-cell subgroup, including memory B cells (MBCs) and plasma cells (PCs)Waldenstrom Megaglobulinemia (WM) is a complex B-cell malignant tumor made up of a unique blend of lymphocytes and plasma cell phenotypesin this study,Weil et alintegrated whole-genome DNA methylation, transcription, mutation and other phenotypes from 35 myD88 mutant WM patients who were associated with normal plasma and B-cell subgroupsstudy found that WM patients could be naturally divided into two groups based on DNA methylation spectrum, associated with normal MBC and PC, and associated with other memory and plasma cell-derived malignanciesSimultaneous analysis of DNA methylation changes during normal and WM development to capture tumor-specific events highlights the inhibition and selective reprogramming of the enhanced subregions and pc-like Chromatin regions in MBC-like WMMBC-like WM low methylation was enriched in the molds of PU1, TCF3 and OCT2 transcription factors, which were associated with increased activity of myD88/TLR pathwayPC-like WM showed significant overall low methylation and selective overexpression of histone genesFinally, the WM subtype exhibits different genetic, phenotypes and clinical characteristicsMBC-like WM carried significantly more cloned CXCR4 mutations, 13q deletions, enlarged spleen and thrombocytopenia, while PC-like WM carried more 6q deletions, 6p amplification, increased frequency of IGHV3 gene, CD38 surface expression and plasma cell differentiation characteristics, this study illustrates a new method of subclassifying Patients with WM using DNA methylation model, and reveals different molecular characteristics among Patients of WM