Journal Article

Mutations associated with age-related clonal hematopoiesis in PMF patients with rapid progression to myelofibrosis

Vogtmann, Julia, Westphal Lina, Lehmann, Ulrich, Kreipe Hans, Muhammad, Faisal, Büsche Guntram, Hasemeier Britta, Bartels, Stephan, Schlue Jerome, Schipper, Elisa

2020

Overview

Besides histopathological findings there are no indicators of increased risk for fibrotic progression in myeloproliferative neoplasms (MPN). Age-related clonal hematopoiesis (ARCH/CHIP) is a frequent finding in the elderly and combinations with MPN driver mutations (JAK2, MPL, and CALR) have been described. To determine the impact of ARCH/CHIP-related mutations for development of fibrosis in primary myelofibrosis (PMF), the mutational status of cases with fibrotic progression from grade 0 to grade 2/3 (n = 77) as evidenced by follow-up bone marrow biopsies (median 6.2 years) was compared with prefibrotic PMF samples without development of fibrosis (n = 27; median follow-up 7.3 years). Frequent ARCH/CHIP-associated mutations (TET2, ASXL1, and DNMT3A) demonstrable at presentation were not connected with fibrotic progression. However, mutations which are rarely found in ARCH/CHIP (SRSF2, U2AF1, SF3B1, IDH1/2, and EZH2) were present in 24.7% of cases with later development of fibrosis and not detectable in cases staying free from fibrosis (P = 0.0028). Determination of the tumor mutational burden (TMB) in a subgroup of cases (n = 32) did not show significant differences (7.68 mutations/MB vs. 6.85 mutations/MB). We conclude that mutations rarely found in ARCH/CHIP provide an independent risk factor for rapid fibrotic progression (median 2.0 years) when manifest already at first presentation.

• Publisher: Nature Publishing Group
• Subject: Age / Arches / Bone marrow / Fibrosis / Geriatrics / Hematopoiesis / Janus kinase 2 / Mutation / Myelofibrosis / Neoplasms / Risk analysis / Risk factors / Subgroups