Hairy cell leukemia (HCL) until recently was characterized as a single blood and bone marrow malignancy, even though clinically at least two pathologies seemed to be at work. This study sought to confirm the clinical observations using genomic evidence. HCL is a chronic mature B-cell malignancy with distinctive immunophenotype, typically expressing CD20, CD22, CD25, CD11c, CD103, CD123, annexin A1 (ANXA1), and tartrate-resistant acid phosphatase (TRAP). Purine analog therapy is highly effective, with most patients achieving durable remissions. HCL- variant (HCLv) was first identified by Cawley et al. (1980) and recently recognized by the World Health Organization as a separate cancer. HCLv lacks CD25, ANXA1, TRAP, and BRAF V600E expression, and patients respond poorly to purine analogs. In order to find detailed biological information involving these two diseases, we studied the genome-wide gene expression and methylation profiles of 75 HCL patient samples; 67 were tested by both methods. Our study results indicate that HCL and HCLv show very distinct gene expression and methylation patterns. Many genes that are differentially expressed are involved in immunological and inflammatory response pathways. Several cancer associated genes such as ANXA1 and FLT3 are down-regulated in HCLv compared to HCL. Correlation patterns between methylation and gene expression for many genes such as ANXA1 suggest that methylation plays an import role in gene expression regulation for these malignancies. This study has begun the process of identifying better biomarkers for disease discrimination between HCL and HCLv and providing potential new targets for strongly needed therapies for HCLv.

Citation Format: Daniel C. Edelman, Holly S. Stevenson, Yonghong Wang, Evgeny Arons, Joshua J. Waterfall, David Petersen, Hong Zhou, Paul S. Meltzer, Robert J. Kreitman. Genomic profiles in gene expression and methylation help define the molecular characteristics of hairy cell leukemia subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4682. doi:10.1158/1538-7445.AM2017-4682