Clonal Hematopoiesis of Indeterminate Potential in High Grade B-Cell Lymphomas: Clinicobiological Associations and Further Insight with Single-Cell Multiomics Analysis

In a population-based cohort of 176 high-grade B-cell lymphoma patients, clonal hematopoiesis of indeterminate potential (CHIP) was detected in 19% and was significantly associated with inferior overall, progression-free, and lymphoma-specific survival (HR = 1.82, p = 0.014), independent of cardiovascular disease, autoimmune disease, or secondary malignancy. Single-cell multiomics (Tapestri, Mission Bio) on tumor material from four patients showed that in two cases, mutations in TP53 and DNMT3A were shared across B-cell, T-cell, and myeloid lineages, supporting a common clonal ancestor preceding lymphomagenesis, while in the other two cases mutations in EZH2 and KIT were largely confined to non-malignant T-cells.