Suzuki Rikio, Onizuka Makoto, Kojima Minoru, Shimada Masako, Okamura Kaori, Fukagawa Satomi, Tsuboi Kosuke, Kikuchi Ako, Kobayashi Hiroyuki, Shintani Ayumi, Ogawa Yoshiaki, Kawada Hiroshi, Hotta Tomomitsu, Ando Kiyoshi
Department of Hematology/Oncology, Tokai University School of Medicine, Kanagawa, Japan.
Int J Hematol. 2007 Dec;86(5):422-8. doi: 10.1007/BF02984000.
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.
含有内部串联重复的FMS样酪氨酸激酶3（FLT3）基因突变（FLT3/ITD）或核仁磷酸蛋白1基因（NPM1）突变被认为是急性髓系白血病（AML）的预后指标。以往研究表明，FLT3/ITD突变提示预后不良，而NPM1突变提示预后较好，但这些研究往往是在选定的患者群体中进行的。我们在本院对一组未经挑选的新诊断AML患者研究了这些突变的临床意义。该组包括年龄≥60岁的患者和体能状态较差的患者。通过聚合酶链反应和测序分析，我们在60例患者中检测到12例（20.0%）有FLT3/ITD突变，7例（11.7%）有NPM1突变。在该人群中，FLT3/ITD突变与较差的预测总生存（OS）概率相关，但差异无统计学意义。相反，无论是所有AML患者还是核型正常的AML患者，野生型NPM1患者的OS均显著高于NPM1突变患者。在这个普通的、未经挑选的AML患者群体中，NPM1突变并非预后良好的指标。
