Developmental subtypes assessed by DNA methylation-iPLEX forecast the natural history of chronic lymphocytic leukemia

We examined the impact of epitype in 1286 CLL patients from 4 independent cohorts representing a comprehensive view of CLL disease course and therapies. We found that epitype significantly predicted TTFT and OS among newly diagnosed CLL patients. Additionally, epitype predicted TTP and OS with 2 common CLL therapies: chemoimmunotherapy and ibrutinib. Epitype retained significance after stratifying by biologically related biomarkers, immunoglobulin heavy chain mutational status, and ZAP70 expression, as well as other common prognostic markers. Furthermore, among several biological traits enriched between epitypes, we found highly biased immunogenetic features, including IGLV3-21 usage in the poorly characterized intermediate-programmed CLL epitype. In summary, Me-iPLEX is an elegant method to assess epigenetic signatures, including robust classification of CLL epitypes that independently stratify patient risk at diagnosis and time of treatment.

Source: Blood - August 21, 2019 Category: Hematology Authors: Giacopelli, B., Zhao, Q., Ruppert, A. S., Agyeman, A., Weigel, C., Wu, Y.-Z., Gerber, M. M., Rabe, K. G., Larson, M. C., Lu, J., Blachly, J. S., Rogers, K. A., Wierda, W. G., Brown, J. R., Rai, K. R., Keating, M., Rassenti, L. Z., Kipps, T. J., Zenz, T., Tags: Lymphoid Neoplasia Source Type: research