U2AF1 pathogenic variants in myeloid neoplasms and precursor states: distribution of co-mutations and prognostic heterogeneity.

Autor: Badar T; Division of Hematology-Oncology and Bone Marrow Transplant Program, Mayo Clinic, Jacksonville, FL, 32224, USA. badar.talha@mayo.edu., Vanegas YAM; Division of Hematology-Oncology and Bone Marrow Transplant Program, Mayo Clinic, Jacksonville, FL, 32224, USA., Nanaa A; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA.; John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, 60612, USA., Foran JM; Division of Hematology-Oncology and Bone Marrow Transplant Program, Mayo Clinic, Jacksonville, FL, 32224, USA., Al-Kali A; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA., Mangaonkar A; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA., Murthy H; Division of Hematology-Oncology and Bone Marrow Transplant Program, Mayo Clinic, Jacksonville, FL, 32224, USA., Alkhateeb HB; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA., Viswanatha D; Division of Hematopathology, Mayo Clinic, Rochester, MN, 55905, USA., He R; Division of Hematopathology, Mayo Clinic, Rochester, MN, 55905, USA., Shah M; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA., Yi CA; Department of Hematology Oncology, Mayo Clinic, Phoenix, AZ, USA., Litzow MR; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA., Gangat N; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA., Tefferi A; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA., Patnaik MM; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA. patnaik.mrinal@mayo.edu.
Jazyk: angličtina
Zdroj: Blood cancer journal [Blood Cancer J] 2023 Sep 21; Vol. 13 (1), pp. 149. Date of Electronic Publication: 2023 Sep 21.
DOI: 10.1038/s41408-023-00922-7
Abstrakt: We have previously recognized the genotypic and prognostic heterogeneity of U2AF1 mutations (MT) in myelofibrosis (MF) and myelodysplastic syndromes (MDS). In the current study, we considered 179 U2AF1-mutated patients with clonal cytopenia of undetermined significance (CCUS; n = 22), MDS (n = 108), MDS/acute myeloid leukemia (AML; n = 18) and AML (n = 31). U2AF1 variants included S34 (60%), Q157 (35%), and others (5%): corresponding mutational frequencies were 45%, 55%, and 0% in CCUS; 57%, 39%, and 4% in MDS; 61%, 33%, and 6% in MDS/AML; and 55%, 35% and 10% in AML (P = 0.17, 0.36 and 0.09), respectively. Concurrent mutations included ASXL1 (37%), BCOR (19%), RUNX1 (14%), TET2 (15%), DNMT3A (10%), NRAS/KRAS (8%), TP53 (8%), JAK2 (5.5%) and SETBP1 (5%). The two most frequent U2AF1 MT were S34F (n = 97) and Q157P (n = 46); concurrent MT were more likely to be seen with the latter (91% vs 74%; P = 0.01) and abnormal karyotype with the former (70% vs 62%; P = 0.05). U2AF1 S34F MT clustered with BCOR (P = 0.04) and Q157P MT with ASXL1 (P = 0.01) and TP53 (P = 0.03). The median overall survival (OS) in months was significantly worse in AML (14.2) vs MDS/AML (27.3) vs MDS (33.7; P = 0.001); the latter had similar OS with CCUS (30.0). In morphologically high-risk disease (n = 49), defined by ≥10% blood or bone marrow blasts (i.e., AML or MDS/AML), median OS was 14.2 with Q157P vs 37.1 months in the presence of S34F (P = 0.008); transplant-adjusted multivariable analysis confirmed the detrimental impact of Q157P (P = 0.01) on survival and also identified JAK2 MT as an additional risk factor (P = 0.02). OS was favorably affected by allogeneic hematopoietic stem cell transplantation (HR: 0.16, 95% CI; 0.04-0.61, P = 0.007). The current study defines the prevalence and co-mutational profiles of U2AF1 pathogenic variants in AML, MDS/AML, MDS, and CCUS, and suggests prognostic heterogeneity in patients with ≥10% blasts.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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