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- Title
Subclones with variants of uncertain clinical significance might contribute to ineffective hemopoiesis and leukemia predisposition.
- Authors
Giudice, Valentina; Serio, Bianca; Errichiello, Santa; Ferrara, Idalucia; Galdiero, Alessandra; Bertolini, Angela; Visconti, Roberta; De Novellis, Danilo; Guariglia, Roberto; Luponio, Serena; Morini, Denise; Corte, Anna Maria Della; Sessa, Anna Maria; Verdesca, Francesco; Langella, Maddalena; Izzo, Barbara; Selleri, Carmine
- Abstract
Background: Splicing modifications, genomic instability, and hypomethylation are central mechanisms promoting myelodysplasia and acute myeloid leukemia (AML). In this real-life retrospective study, to elucidate pathophysiology of clonal hemopoiesis in hematological malignancies, we investigated clinical significance of mutations in leukemia-related genes of known pathogenetic significance and of variants of uncertain clinical significance (VUS) in a cohort of patients with MDS and AML. Methods: A total of 59 consecutive subjects diagnosed with MDS, 48 with AML, and 17 with clonal cytopenia with unknown significance were screened for somatic mutations in AML-related genes by next-generation sequencing. Results: We showed that TET2, SETBP1, ASXL1, EZH2, RUNX1, SRSF2, DNMT3A, and IDH1/2 were commonly mutated. MDS patients also showed a high genetic complexity, especially for SETBP1. Moreover, the presence of SETBP1 wild-type or two or more simultaneous VUS variants identified a subgroup of AML and MDS patients with better outcome, while the presence of single SETBP1 VUS variant was related to a worse prognosis, regardless TET2 mutational status. Conclusions: In conclusions, we linked both pathogenic and VUS variants in AML-related genes to clonal hematopoiesis; therefore, we proposed to consider those variants as prognostic markers in leukemia and myelodysplasia. However, further studies in larger prospective cohorts are required to validate our results.
- Subjects
HEMATOPOIESIS; LEUKEMIA; ACUTE myeloid leukemia; HEMATOLOGIC malignancies; PROGNOSIS
- Publication
European Journal of Haematology, 2023, Vol 111, Issue 5, p729
- ISSN
0902-4441
- Publication type
Article
- DOI
10.1111/ejh.14069