Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 619

Over the past few years, our understanding of the genetic basis for MDS has expanded significantly. The mutations observed in MSD involve genes that encode diverse proteins that play roles in various cellular pathways such as RNA splicing (SF3B1, SRSF2, U2AF1, ZRSR2), DNA methylation (DNMT3A, TET2, IDH1, IDH2), cohesion complex (STAG2), transcriptional regulation (TP53, RUNX1, GATA2), chromatin modification (ASXL1, EZH2), and signal transduction (JAK2, KRAS, NRAS, CBL).^46,47

Mutations in the Ten‐Eleven Translocation‐2 gene (TET2) were recently identified in MDS and other myeloid neoplasms.^48‐50 TET2 mutations occur in 10–26% of MDS patients. The enzyme converts methylcytosine to hydroxymethylcytosine and thus may play a role in DNA methylation and may predict the response to hypomethylating agents.⁵¹

The spliceosome gene SF3B1 is a recurrent mutation in MDS and is associated with ring sideroblasts.⁵² SF3B1 mutation is an early event in MDS pathogenesis and predicts a favourable prognosis.⁵³ TP53 mutations are detected in approximately 5–20% of cases in MDS⁵⁴ and are associated with higher‐risk MDS, therapy‐related MDS, and MDS with complex cytogenetics.