title: TP53 mutations in older adults with acute myeloid leukemia.
abstract: The net benefits of induction therapy for older adults with acute myeloid leukemia (AML) remain controversial. Because AML in older adults is a heterogeneous disease, it is important to identify those who are unlikely to benefit from induction therapy based on information available at the initial assessment. We used next-generation sequencing to analyze TP53 mutation status in AML patients aged 60 years or older, and evaluated its effects on outcomes. TP53 mutations were detected in 12 of 77 patients (16 %), and there was a significant association between TP53 mutations and monosomal karyotype. Patients with TP53 mutations had significantly worse survival than those without (P = 0.009), and multivariate analysis identified TP53 mutation status as the most significant prognostic factor for survival. Neverthelsess, TP53-mutated patients had a 42 % chance of complete remission and a median survival of 8.0 months, which compares favorably with those who did not undergo induction therapy, even in the short term. These results suggest that screening for TP53 mutations at diagnosis is useful for identifying older adults with AML who are least likely to respond to chemotherapy, although the presence of this mutation alone does not seem to justify rejecting induction therapy.
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan. myanada@fujita-hu.ac.jp.
authors.forename: Masamitsu
authors.identifier: http://orcid.org/0000-0003-1602-9775
authors.initials: M
authors.lastname: Yanada
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Iba
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Akinao
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Inaguma
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Masutaka
authors.initials: M
authors.lastname: Tokuda
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Morishima
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Tadaharu
authors.initials: T
authors.lastname: Kanie
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mizuta
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Akatsuka
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Emi
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Acute myeloid leukemia; Monosomal karyotype; Older adults; TP53