Prognostic Significance of FLT3 Internal Tandem Duplication and NPM1 Mutations in Acute Myeloid Leukemia in an Unselected Patient Population

Mutations in the fms-like tyrosine kinase 3 (FLT3) gene containing an internal tandem duplication (FLT3/ITD) or mutations in the nucleophosmin 1 gene (NPM1) are thought to be prognostic indicators in acute myeloid leukemia (AML). Previous studies suggested that FLT3/ITD mutation indicates a poor pro...

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Bibliographic Details
Published in:International journal of hematology 2007-12, Vol.86 (5), p.422-428
Main Authors: SUZUKI, Rikio, ONIZUKA, Makoto, OGAWA, Yoshiaki, KAWADA, Hiroshi, HOTTA, Tomomitsu, ANDO, Kiyoshi, KOJIMA, Minoru, SHIMADA, Masako, OKAMURA, Kaori, FUKAGAWA, Satomi, TSUBOI, Kosuke, KIKUCHI, Ako, KOBAYASHI, Hiroyuki, SHINTANI, Ayumi
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Disease-Free Survival
DNA Mutational Analysis
Female
fms-Like Tyrosine Kinase 3 - genetics
Hematologic and hematopoietic diseases
Humans
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - mortality
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Middle Aged
Mutation
Nuclear Proteins - genetics
Polymerase Chain Reaction
Predictive Value of Tests
Survival Rate
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Summary:Mutations in the fms-like tyrosine kinase 3 (FLT3) gene containing an internal tandem duplication (FLT3/ITD) or mutations in the nucleophosmin 1 gene (NPM1) are thought to be prognostic indicators in acute myeloid leukemia (AML). Previous studies suggested that FLT3/ITD mutation indicates a poor prognosis and that NPM1 mutation indicates a more favorable one, but these studies were often performed with selected patient populations. We investigated the clinical significance of these mutations at our institution with an unselected group of patients with newly diagnosed AML. This group included patients > or =60 years old and those with a poor performance status. Using polymerase chain reaction and sequencing analyses, we detected FLT3/ITD mutations in 12 patients (20.0%) and NPM1 mutations in 7 patients (11.7%) among a group of 60 patients. There was a nonsignificant trend for FLT3/ITD mutation to be associated with a poorer predicted overall survival (OS) probability in this population. In contrast, OS was significantly higher in patients with wild-type NPM1 than in patients with NPM1 mutation, both for all AML patients and for AML patients with a normal karyotype. In this general and unselected AML patient population, NPM1 mutation was not a prognostic indicator of a favorable outcome.
ISSN:0925-5710
1865-3774
DOI:10.1532/IJH97.07116