The clinical importance of DNA methylation signatures in chronic lymphocytic leukemia patients treated with chemo-immunotherapy

Variations in the CLL DNA methylome reflect modifications that occur during normal B cell maturation, along with IGHV mutated (M-CLL) and unmutated CLL (U-CLL), retaining an imprint of the DNA methylation signature of memory (m-CLL) and naive B cells (n-CLL), respectively, with a third intermediate epigenetic subgroup (i-CLL) (1-3). To further test the clinical utility of DNA methylation signatures, we performed the first analysis of patients entering clinical trials; we tested treatment-naive CLL patients [n=605] randomized to CLL4 (chemotherapy, CT) (4), ARCTIC and ADMIRE (both chemo-immunotherapy, CIT) (5, 6). We identified n-, i- and m-CLL in 49.3% (n=299), 32.0% (n=195) and 18.5% (n=112) of our patients, respectively. Fewer m-CLL patients were identified in our study compared to published data reflecting the progressive nature of our cohort, with 80% (n=245/305, P Citation Format: Tomasz K. Wojdacz, Harindra E. Amarasinghe, Matthew JJ Rose-Zerilli, Alice Beattie, Jade Forster, Latha Kadalayil, Stuart Blakemore, Helen Parker, Marta Larrayoz, Ruth Clifford, Zadie Davis, Monica Else, Dena Cohen, Andrew J. Steele, Richard Rosenquist, Andrew Collins, Andrew Pettitt, Peter Hillmen, Christoph Plass, Anna Schuh, Daniel Catovsky, David G. Oscier, Christopher C. Oakes, Jonathan C. Strefford. The clinical importance of DNA methylation signatures in chronic lymphocytic leukemia patients treated with chemo-immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3306.