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Cited by 102Acute Myeloid Leukemia ResearchRetinoids in leukemia and cellular processesCancer Genomics and Diagnostics

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

Sasaki, Koji, Kanagal‐Shamanna, Rashmi, Montalban‐Bravo, Guillermo, Assi, Rita, Jabbour, Elias, Ravandi, Farhad, Kadia, Tapan, Pierce, Sherry +7 more·2020·Cancer
DOI 10.1002/cncr.32566
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Abstract

Background: 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). Methods: 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%. Results: 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. Conclusions: The VAF of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 mutations is associated with worse prognosis in patients with newly diagnosed AML.

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  • TP53 gene mutations are detected in approximately 10%-20% of patients with de novo MDS or AML and 30%-40% of patients with therapy-related disease.

    “TP53 gene mutations are detected in approximately 10%-20% of patients with de novo myelodysplastic syndromes (MDS)1-4 or acute myeloid leukemia (AML)5,6 and 30%-40% of patients with therapy-related disease.7”

    From Eprenetapopt (APR-246) and Azacitidine in <i>TP53</i> -Mutant Myelodysplastic Syndromes (2021) · cites this paper as [5]

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Authors
Sasaki, K., Kanagal‐Shamanna, R., Montalban‐Bravo, G., Assi, R., Jabbour, E., Ravandi, F., Kadia, T., Pierce, S., Takahashi, K., Nogueras Gonzalez, G., Patel, K., Soltysiak, K. A., Cortes, J., Kantarjian, H. M., & Garcia‐Manero, G.
Affiliations
  • Tokyo Medical and Dental University (JP)
  • The University of Texas MD Anderson Cancer Center (US)
  • Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas
  • Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston Texas
Corresponding author
Garcia‐Manero, Guillermo
ORCID
Venue
Cancer
Publisher
Wiley
Published
2019-11-19
Volume
126
Issue
4
Pages
765-774
ISSN
  • 0008-543X (ISSN-L)
  • 1097-0142
DOI
10.1002/cncr.32566
OpenAlex
W2989809064
Cited by
101
References
23
Citations by year
2026: 11 · 2025: 7 · 2024: 12 · 2023: 23 · 2022: 17 · 2021: 21 · 2020: 9
FWCI
8.30
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Cancer (publishedVersion)
  • PubMed (publishedVersion)
Funders
University of Texas MD Anderson Cancer Center (CA016672)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
acute myeloid leukemia, variant allele frequency, ASXL1 mutation, DNMT3A mutation, JAK2 mutation, TET2 mutation, TP53 mutation, NPM1 mutation, complete response, overall survival, prognostic factors, FLT3 inhibitors, dysplasia, white blood cell count, age, bone marrow
MeSH terms
DNA Methyltransferase 3A, Nucleophosmin, Acute Disease, DNA (Cytosine-5-)-Methyltransferases, DNA-Binding Proteins, Female, Gene Frequency, Humans, Leukemia, Myeloid, Male, Middle Aged, Mutation, Nuclear Proteins, Prognosis, Proto-Oncogene Proteins, Repressor Proteins, Retrospective Studies, Biomarkers, Tumor, Tumor Suppressor Protein p53, Genetic Predisposition to Disease, Dioxygenases, Kaplan-Meier Estimate, Janus Kinase 2, High-Throughput Nucleotide Sequencing

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