Landscape and clinical impact of NOTCH mutations in newly diagnosed acute myeloid leukemia. Issue 2 (12th November 2022)

• Record Type: Journal Article
• Authors: Han, Haohao; Yao, Yifang; Wang, Hong; Zhou, Meng; Zhang, Ziyan; Xu, Xiaoyan; Qi, Jiaqian; Liu, Yuejun; Wu, Depei; Han, Yue
• Is Part Of: Cancer. Volume 129:Issue 2(2023)
• Page Start: 245
• Page End: 254
• Publication Date: 2022-11-12
• Subjects: AML -- mutation -- NOTCH -- prognosis -- relapse; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.34534
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract: Background: NOTCH mutations (NOTCH mut ) are recognized as major oncogenic drivers associated with controversial clinical impact on T‐cell acute lymphoblastic leukemia (T‐ALL), whereas their clinical value on acute myeloid leukemia (AML) is poorly defined. Methods: A study involving 878 consecutive newly diagnosed patients with AML was undertaken in an institution with available clinical data to unravel the impact of NOTCH mut on prognosis. Results: In the study, NOTCH mut were discovered in 3.6% (32/878) of included patients with AML and composed substitution‐missense, frameshift mutation, substitution‐nonsense, and insertion‐in frame. These mutations were more commonly associated with low platelet (29 vs 42 × 10 9 /L, p = .024) count and coexisted with BCOR/BCORL1 (15.6% vs 3.2%, p = .001), DNMT3A (28.1% vs 12.5%, p = .021), and MPL (9.4% vs 0.8%, p = .004) mutations compared with NOTCH wild‐type (NOTCH wt ). No significant difference was observed in treatment responses between NOTCH mut and NOTCH wt . The presence of NOTCH mut was associated with worse overall survival ([OS], 1 year‐OS: 68.0% vs 84.2%; 3 year‐OS: 48.3% vs 59.6%; p = .059) and relapse‐free survival ([RFS], 1 year‐RFS: 78.3% vs 85.4%; 3 year‐RFS: 54.5% vs 76.9%; p = .018), especially within the European Leukemia Net 2017 intermediate‐risk group. Furthermore, allogeneic hematopoietic stem cell transplantation might abrogate the dismal impact of NOTCH mut on RFS. In multivariate analysis, NOTCH mut were found to be an independent factor negatively influencing RFS (hazard ratio, 2.153; 95% CI, 1.166‐3.975; p = .014). Conclusion: This study suggests that NOTCH mut may serve as an indicator for poor prognosis of AML. Plain language summary: Although NOTCH mutations (NOTCH mut ) are well studied in T‐cell acute lymphoblastic leukemia (T‐ALL), less is known about their incidence and prognostic implications in acute myeloid leukemia (AML). A total of 878 newly diagnosed patients with AML was retrospectively analyzed; it was found that the frequency of NOTCH mut was relatively low but was associated with an adverse prognosis. Abstract : A retrospective study in a large cohort of 878 patients with acute myeloid leukemia (AML) was performed, and the study suggested that NOTCH mutations may serve as indicators for poor prognosis of AML.