TFH lymphoma and associated clonal hematopoiesis

Abstract

T‑follicular helper (TFH) cell lymphoma (TFHL) is alymphoma of mature Tcells with phenotypic characteristics and gene expression signature of TFH cells. The lymphoma harbors recurrent mutations of RHOAG17V, IDH2R172, TET2 and DNMT3A. Whereas RHOAG17V and IDH2R172 are almost exclusively found in this entity, TET2 and DNMT3A mutations occur in abroad variety of hematological neoplasms and are the most frequently affected genes in clonal hematopoiesis (CH). CH in humans shows aprogression rate to overt hematologic neoplasia of about 0.5to 1% per year, depending on clone size, number of mutations and affected genes. In 2018, the first case was described in which alymphoid (TFHL) and myeloid (acute myeloid leukemia) neoplasm arose from acommon mutated progenitor cell with shared mutations and additional private mutations. In recent years, further studies showed in up to 70% of patients with TFHL the occurrence of identical mutations of TET2 and/or DNMT3A in the myeloid cells, irrespective of bone marrow involvement, indicating aprominent role of CH in the pathogenesis of TFHL. In up to 18%, these patients show also additional synchronous or metachronous overt myeloid neoplasms, often with private myelodysplastic-type mutations, most often myelodysplastic syndrome, chronic myelomonocytic leukemia and acute myeloid leukemia. Recently, there is also evidence for two distinct lymphoid neoplasms arising from CH. TFH lymphoma cases with antecedent or concomitant hematologic neoplasm often show high variant allelic frequencies of TET2 and often more than one mutation, suggesting arole for surveillance in these patients.