In:
Acta Haematologica, S. Karger AG, Vol. 144, No. 6 ( 2021), p. 649-659
Abstract:
〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 This study aimed to identify genetic predictors of treatment response and survival in patients with myeloid neoplasms treated with hypomethylating agents (HMAs). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We performed next-generation sequencing on bone marrow aspiration samples of 59 patients diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome with excess blasts-2, or chronic myelomonocytic leukemia and treated with decitabine or azacitidine as a frontline therapy. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 A single gene with the most common mutations was 〈 i 〉 TP53 〈 /i 〉 (14 of 59 patients), and mutations in RAS pathway-related genes including 〈 i 〉 KRAS 〈 /i 〉 , 〈 i 〉 NRAS 〈 /i 〉 , 〈 i 〉 FLT3 〈 /i 〉 , 〈 i 〉 PTPN11 〈 /i 〉 , 〈 i 〉 CBL 〈 /i 〉 , and 〈 i 〉 KIT 〈 /i 〉 were found in 28.8% of patients. The overall response rate to HMAs was 33.9%. Predictive factors for a poor response were an age & #x3e;75 years ( 〈 i 〉 p 〈 /i 〉 = 0.007), 3 or more gene mutations ( 〈 i 〉 p 〈 /i 〉 = 0.004), mutations in RAS pathway-related genes ( 〈 i 〉 p 〈 /i 〉 = 0.033), and a mutated 〈 i 〉 NRAS 〈 /i 〉 gene ( 〈 i 〉 p 〈 /i 〉 = 0.042). An age & #x3e;75 years (hazard ratio 2.946), diagnosis of AML (hazard ratio 2.915), and mutations in 〈 i 〉 NRAS 〈 /i 〉 (hazard ratio 4.440) were identified as poor prognostic factors for survival. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 In conclusion, mutations in RAS pathway-related genes were predictors of a poor response to HMAs. Particularly, mutated 〈 i 〉 NRAS 〈 /i 〉 was associated with inferior survival rates.
Type of Medium:
Online Resource
ISSN:
0001-5792
,
1421-9662
Language:
English
Publisher:
S. Karger AG
Publication Date:
2021
detail.hit.zdb_id:
1481888-7
detail.hit.zdb_id:
80008-9
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