Nucleophosmin mutation in Southeast Asian acute myeloid leukemia:: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations
Nucleophosmin mutation in Southeast Asian acute myeloid leukemia:: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations
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DOI：
10.3324/haematol.12937
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发表时间：
2008-10-01
期刊：
影响因子：
--
通讯作者：
Auewarakul, Chirayu U.
中科院分区：
文献类型：
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作者：
Boonthimat, Chetsada;Thongnoppakhun, Wanna;Auewarakul, Chirayu U.
对400例东南亚白血病患者进行了NPM1基因突变检测，发现105例(26.25%)急性髓系白血病可检出NPM1突变，而急性淋巴细胞白血病和慢性髓系白血病均未检出NPM1突变。共鉴定出8个新突变和5个已知突变。所有预测的新蛋白都分享了最后5个氨基酸VSLRK，并获得了与已知变体类似的核输出信号基序。高龄、高白细胞和高血小板计数、正常细胞遗传学和CD34阴性与NPM1突变相关。突变型NPM1中Flt3突变的发生率(56.8%)高于野生型(25.6%)，而RAS和AML1突变很少发现。基于NPM1/Flt3突变状态的总体生存分析显示，NPM1阳性/flt3阴性亚组的结果更好。我们的结论是：1)NPM1突变是核型正常的东南亚急性髓系白血病的共同遗传标志；2)NPM1突变主要与Flt3突变共存，而不是RAS或AML1；iii)Flt3突变对NPM1突变患者的预后有负面影响。
NPM1 mutations were investigated in 400 Southeast Asian leukemia patients and were detectable in 105 cases (26.25%) of acute myeloid leukemia but in no cases of acute lymphoid leukemia or chronic myeloid leukemia. Eight novel and 5 known mutations were identified. All predicted novel proteins shared the last five amino acids VSLRK with the similar gain of nuclear exporting signal motif as known variants. Older age, high white blood cell and platelet counts, normal cytogenetics, and CD34-negativity were associated with NPM1 mutation. FLT3 mutation was more frequent in mutant NPM1 than wild-type cases (56.8% vs. 25.6%) whereas RAS and AML1 mutations were rarely found. Overall survival analysis based on the NPM1/FLT3 mutational status revealed a better outcome for the NPM1-positive/FLT3-negative subgroup. We conclude that: i) NPM1 mutation represents a common genetic hallmark in Southeast Asian acute myeloid leukemia with a normal karyotype; ii) NPM1 mutants coexisted mainly with FLT3 mutants, but not RAS or AML1; iii) FLT3 mutation had a negative prognostic impact on patients with mutant NPM1.