The combined epigenetic and immunogenetic ELC^LV3-21 signature. Using the Me-iPLEX methylation assay, HC-MBL and CLL were divided into LP, IP, and HP epitypes. The IGVL3-21^R110 status was assessed by sequencing in IP MBL/CLL. IP cases carrying the IGVL3-21^R110 mutation were grouped with the LP epitype into the ELC^LV3-21 high-risk group, and IGVL3-21^R110-wild-type IP cases were merged with the HP epitype into the ELC^LV3-21 low-risk group.