ELC^LV3-21 classification of MBL. (A) Heat map displaying DNA methylation of loci used in determining epitype by the CLL Methylation-iPLEX (Me-iPLEX) assay. Epitype random forest classifier and IGLV3-21^R110 calls are indicated above. Estimation of sample purity was determined by the Me-iPLEX assay. (B) ELC^LV3-21 risk groups were defined by first determining epitype followed by sequencing of immunoglobulin light chain (IGL) gene rearrangements. Individuals with IGLV3-21^R110 rearrangements were combined with the LP epitype to generate the ELC^LV3-21 high-risk group, and those individuals with light chain rearrangements or lacking the R110 mutation were combined with the HP epitype to produce the ELC^LV3-21 low-risk group. (C,D) Cumulative incidence of time to CLL progression (C) and time to first treatment (D) in individuals with MBL separated by ELC^LV3-21 risk status.