Epigenetic Signature Could Improve Prediction of MBL Progression

Researchers have harnessed an epigenetic and immunogenetic signature to better identify patients with monoclonal B-cell lymphocytosis (MBL) that will progress to chronic lymphocytic leukemia (CLL) requiring therapy. This signature improved prediction of clinical outcomes for these patients compared with other established prognostic indicators.

Recently, patients with CLL classified as the intermediate epitype were found to be enriched for high-risk immunoglobulin lambda variable (IGLV) 3-21 rearrangement, adversely impacting outcomes. In this study, researchers identified 219 patients diagnosed with MBL at the Mayo Clinic between 2000 and 2020 and generated an epigenetic and light chain immunoglobulin (ELC^LV3-21) signature to classify patients with MBL.

An ELC^LV3-21 high-risk group was formed by merging individuals with the IP epitype (intermediate) who have IGLV3-21^R110 rearrangements with those in the poor-risk (LP) epitype.

The ELC^LV3-21  high-risk signature distinguished those with MBL with a high probability of progression; risk of progression was 39.9% at five years and 71.1% at 10 years. In contrast, risk of progression among the ELC^LV3-21  low-risk signature group was 3.4% at five years and 11.3% at 10 years.

“The identification of a precursor condition such as MBL can cause considerable anxiety and presents an uncertain future,” the researchers wrote. “Our findings demonstrate that ELC^LV3-21 is a powerful predictor of progression from MBL to CLL and to CLL requiring treatment over a period that surpasses life expectancy for most diagnosed individuals.”

Accuracy of predicting time to therapy for those with MBL was improved using the signature as compared with other established prognostic indicators, including IGHV mutation status and the CLL International Prognostic Index, the researchers noted.

Finally, compared with 226 patients with CLL, those with MBL considered to be ELC^LV3-21  high risk had significantly shorter time to therapy (P=.003) and reduced overall survival (P=.03) compared with low-risk individuals with CLL.

“We propose that ELC^LV3-21 alone or in combination with other established markers should be included in future validation studies to forecast outcomes of individuals identified with elevated clonal B cells irrespective of cell count at diagnosis,” the researchers concluded.

Reference

Abdelbaky SB, Giacopelli B, Rabe KG, et al. Prediction of outcomes for high-count monoclonal B lymphocytosis using an epigenetic and immunogenetic signature. Blood. 2024;143(17):1752-1757. doi:10.1182/blood.2023022180