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High NPM1-mutant allele burden at diagnosis predicts unfavorable outcomes in de novo AML.
Patel, Sanjay S; Kuo, Frank C; Gibson, Christopher J; Steensma, David P; Soiffer, Robert J; Alyea, Edwin P; Chen, Yi-Bin A; Fathi, Amir T; Graubert, Timothy A; Brunner, Andrew M; Wadleigh, Martha; Stone, Richard M; DeAngelo, Daniel J; Nardi, Valentina; Hasserjian, Robert P; Weinberg, Olga K.
Afiliação
  • Patel SS; Department of Pathology, Brigham and Women's Hospital, Boston, MA.
  • Kuo FC; Department of Pathology, Brigham and Women's Hospital, Boston, MA.
  • Gibson CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
  • Steensma DP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
  • Soiffer RJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
  • Alyea EP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
  • Chen YA; Massachusetts General Hospital Cancer Center, Boston, MA.
  • Fathi AT; Massachusetts General Hospital Cancer Center, Boston, MA.
  • Graubert TA; Massachusetts General Hospital Cancer Center, Boston, MA.
  • Brunner AM; Massachusetts General Hospital Cancer Center, Boston, MA.
  • Wadleigh M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
  • Stone RM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
  • DeAngelo DJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
  • Nardi V; Department of Pathology, Massachusetts General Hospital, Boston, MA; and.
  • Hasserjian RP; Department of Pathology, Massachusetts General Hospital, Boston, MA; and.
  • Weinberg OK; Department of Pathology, Brigham and Women's Hospital, Boston, MA.
Blood ; 131(25): 2816-2825, 2018 06 21.
Article em En | MEDLINE | ID: mdl-29724895
Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 World Health Organization classification and is associated with a favorable prognosis. Although previous studies have evaluated NPM1 in a binary fashion, little is known about the significance of its mutant allele burden at diagnosis, nor has the effect of comutations (other than FLT3) been extensively evaluated. We retrospectively used targeted sequencing data from 109 patients with de novo AML with mutated NPM1 to evaluate the potential significance of NPM1 variant allele frequency (VAF), comutations, and clinical parameters with regard to patient outcomes. We observed that high NPM1 VAF (uppermost quartile) correlated with shortened overall survival (median, 12.1 months vs not reached; P < .0001) as well as event-free survival (median, 7.5 vs 65.44 months; P < .0001) compared with the other NPM1-mutated cases. In both univariate and multivariable analyses, high NPM1 VAF had a particularly adverse prognostic effect in the subset of patients treated with stem-cell transplantation in first remission (P = .0004) and in patients with mutated DNMT3A (P < .0001). Our findings indicate that the prognostic effect of NPM1 mutation in de novo AML may be influenced by the relative abundance of the mutated allele.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Leucemia Mieloide Aguda / Frequência do Gene / Mutação Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Leucemia Mieloide Aguda / Frequência do Gene / Mutação Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article