CD6 expression is an independent predictor of time to first treatment in chronic lymphocytic leukemia

Abstract

CD6 is a lymphocytic receptor expressed by all T cells and a subset of B and NK cells. It physically associates with the antigen-specific clonotypic receptor of T (TCR) cells, where it modulates the activation and differentiation signals delivered along lymphocyte development and upon peripheral antigen recognition. CD6 is also expressed in some B cell malignancies (e.g., chronic lymphocytic leukemia, CLL), though its biological role and clinical performance is largely unknown. To this end, we have evaluated the potential impact of CD6 differential expression in a CLL patient cohort. 270 CLL patient histories from the CLL-ES project with available RNA-Seq data have been analysed. High CD6 expression was found to be associated with mutated IGHV status and predictive of longer time to first treatment in a uni- and multivariable model (10-year probability of receiving treatment was 33 vs. 55 % in CD6hi and CD6lo groups, respectively, P = 0.0003) along with the lymphocyte count and the CLL International Prognostic Index. Further gene set enrichment analyses (GSEA) showed association of high CD6 expression with downregulation of MYC-regulated, mitotic spindle-related and RNA splicing-associated genes, all positively related to cancer progression. Interestingly, CD38, a widely studied adverse prognostic marker in CLL, was significantly downregulated in the CD6 high group, in agreement with flow cytometry data. These results reinforce the notion that CD6 may play a pivotal role in neoplastic B cell biology and lay the ground to further explore CD6 expression in the context of CLL prognoses.