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

被引：8

作者：

Badar, Talha ^{[1
,2
]}

Vanegas, Yenny A. Moreno ^{[1
,2
]}

Nanaa, Ahmad ^{[3
,4
]}

Foran, James M. ^{[1
,2
]}

Al-Kali, Aref ^{[3
]}

Mangaonkar, Abhishek ^{[3
]}

Murthy, Hemant ^{[1
,2
]}

Alkhateeb, Hassan B. ^{[3
]}

Viswanatha, David ^{[5
]}

He, Rong ^{[5
]}

Shah, Mithun ^{[3
]}

Yi, Cecilia Arana ^{[6
]}

Litzow, Mark R. ^{[3
]}

Gangat, Naseema ^{[3
]}

Tefferi, Ayalew ^{[3
]}

Patnaik, Mrinal M. ^{[3
]}

机构：

[1] Mayo Clin, Div Hematol Oncol, Jacksonville, FL 32224 USA

[2] Mayo Clin, Bone Marrow Transplant Program, Jacksonville, FL 32224 USA

[3] Mayo Clin, Div Hematol, Rochester, MN 55905 USA

[4] John H Stroger Jr Hosp Cook Cty, Chicago, IL 60612 USA

[5] Mayo Clin, Div Hematopathol, Rochester, MN 55905 USA

[6] Mayo Clin, Dept Hematol Oncol, Phoenix, AZ USA

来源：

BLOOD CANCER JOURNAL | 2023年 / 13卷 / 01期

关键词：

MYELODYSPLASTIC SYNDROME; DIAGNOSIS; IMPACT;

D O I：

10.1038/s41408-023-00922-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：7

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