Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia
Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia
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DOI：
10.1182/blood-2005-04-1733
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发表时间：
2005-10-15
期刊：
影响因子：
20.3
通讯作者：
Naoe, T
中科院分区：
文献类型：
--
作者：
Suzuki, T;Kiyoi, H;Naoe, T
最近，在急性髓性白血病（AML）中报道了核磷蛋白基因（NPM1）的体细胞突变，这种突变改变了产物的亚细胞定位。我们分析了257例AML患者中NPM1突变与细胞遗传学、FLT3、NRAS和TP53突变以及MLL基因部分串联重复（MLL- td）的临床意义。我们在257例患者中的64例（24.9%）中发现了NPM1突变，包括4个新的序列变异。NPM1突变与FLT3的正常核型、内部串联重复（ITD）和D835突变相关，但与其他突变无关。在接受日本成人白血病研究组方案治疗的190例无M3法美英（FAB）亚型患者中，多变量分析显示NPM1突变是实现完全缓解的有利因素，但与高复发率相关。对诊断和复发时获得的39个配对样本进行序列分析显示，在17例诊断时具有NPM1突变的患者中，有2例在复发时丢失了NPM1突变。这些结果表明，NPM1突变不一定是白血病发生过程中的早期事件，或者具有NPM1突变的白血病克隆对化疗敏感。
Recently, somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, have been reported in acute myeloid leukemia (AML). We analyzed the clinical significance of NPM1 mutations in comparison with cytogenetics, FLT3, NRAS, and TP53 mutations, and a partial tandem duplication of the MLL gene (MLL-TD) in 257 patients with AML. We found NPM1 mutations, including 4 novel sequence variants, in 64 of 257 (24.9%) patients. NPM1 mutations were associated with normal karyotype and with internal tandem duplication (ITD) and D835 mutations in FLT3, but not with other mutations. In 190 patients without the M3 French-American-British (FAB) subtype who were treated with the protocol of the Japan Adult Leukemia Study Group, multivariate analyses showed that the NPM1 mutation was a favorable factor for achieving complete remission but was associated with a high relapse rate. Sequential analysis using 39 paired samples obtained at diagnosis and relapse showed that NPM1 mutations were lost at relapse in 2 of the 17 patients who had NPM1 mutations at diagnosis. These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy.