We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Impact of the variant allele frequency of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 on the outcomes of patients with newly diagnosed acute myeloid leukemia.
- Authors
Sasaki, Koji; Kanagal‐Shamanna, Rashmi; Montalban‐Bravo, Guillermo; Assi, Rita; Jabbour, Elias; Ravandi, Farhad; Kadia, Tapan; Pierce, Sherry; Takahashi, Koichi; Nogueras Gonzalez, Graciela; Patel, Keyur; Soltysiak, Kelly A.; Cortes, Jorge; Kantarjian, Hagop M.; Garcia‐Manero, Guillermo; Kanagal-Shamanna, Rashmi; Montalban-Bravo, Guillermo; Garcia-Manero, Guillermo
- Abstract
<bold>Background: </bold>The impact of the allelic burden of ASXL1, DNMT3A, JAK2, TET2, and TP53 mutations on survival remains unclear in patients with newly diagnosed acute myeloid leukemia (AML).<bold>Methods: </bold>The authors assessed bone marrow aspirates from 421 patients with newly diagnosed AML using next-generation sequencing for ASXL1, DNMT3A, JAK2, TET2, and TP53 mutations, defined as the presence of mutations in ASXL1, DNMT3A, JAK2, TET2, or TP53 with a minimum variant allele frequency (VAF) of 5%.<bold>Results: </bold>A total of 71 patients (17%) had ASXL1 mutations, 104 patients (25%) had DNMT3A mutations, 16 patients (4%) had JAK2 mutations, 82 patients (20%) had TET2 mutations, and 86 patients (20%) had TP53 mutations. Among patients with each mutation, the median VAF of ASXL1 was 34.31% (range, 1.17%-58.62%), the median VAF of DNMT3A was 41.76% (range, 1.02%-91.66%), the median VAF of JAK2 was 46.70% (range, 10.4%-71.7%), the median VAF of TET2 was 42.78% (range, 2.26%-95.32%), and the median VAF of TP53 was 45.47% (range, 1.15%-93.74%). The composite complete response rate was 60%, and was 77% in patients with AML with and without ASXL1, DNMT3A, JAK2, TET2, or TP53 mutations, respectively (P = .006); the median overall survival was 11 months and 27 months, respectively (P < .001). Multivariate analysis identified age; an antecedent history of dysplasia; white blood cell count; adverse cytogenetic risk; previous treatment with an FLT3 inhibitor; and the VAF of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 mutations by next-generation sequencing as prognostic factors for overall survival.<bold>Conclusions: </bold>The VAF of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 mutations is associated with worse prognosis in patients with newly diagnosed AML.
- Subjects
ACUTE myeloid leukemia; GENE frequency; LEUKOCYTE count
- Publication
Cancer (0008543X), 2020, Vol 126, Issue 4, p765
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.32566