Non-A type nucleophosmin 1 gene mutation predicts poor clinical outcome in de novo adult acute myeloid leukemia: differential clinical importance of NPM1 mutation according to subtype
Non-A type nucleophosmin 1 gene mutation predicts poor clinical outcome in de novo adult acute myeloid leukemia: differential clinical importance of NPM1 mutation according to subtype
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DOI：
10.1007/s12185-009-0350-1
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发表时间：
2009-07-01
影响因子：
2.1
通讯作者：
Kim, Byoung Kook
中科院分区：
文献类型：
--
作者：
Koh, Youngil;Park, Juwon;Kim, Byoung Kook
已知核磷蛋白基因（NPM 1）突变与缺乏FLT 3内部串联重复（FLT 3-ITD）的AML患者的良好预后相关。最近，NPM 1基因突变的报告以外的A型，但其临床意义并不清楚。对106例缺乏FLT 3-ITD的初治AML患者进行了回顾性病历审查，这些患者在1997年至2007年期间在韩国的三个中心接受了诱导化疗。对诱导化疗前患者血液样本的基因组DNA进行NPM 1直接测序和FLT 3-ITD的RT-PCR，以检测突变。18例患者中检测到NPM 1突变，其中13例为A型突变，5例为非A型突变。CR、CR 1-D和OS总体上不因NPM 1突变状态而异。但是，与NPM 1野生型和NPM 1 A型突变相比，非A型NPM 1突变与较短的CR 1-D相关（p = 0.004）。与NPM 1野生型患者和NPM 1 A型突变体相比，非A型突变体的OS较短（p = 0.001）。NPM 1的突变类型对于缺乏FLT 3-ITD的新发AML的预后是重要的。非A型NPM 1突变是一个不良预后因素。
Mutations of nucleophosmin gene (NPM1) are known to be related to good prognosis in AML patients lacking FLT3 internal tandem duplication (FLT3-ITD). Recently, NPM1 mutations other than type A were reported, but their clinical significance is not well known. Retrospective medical record review of 106 de novo AML patients lacking FLT3-ITD, who received induction chemotherapy from three centers in Korea between 1997 and 2007, was performed. Direct sequencing of NPM1 and RT-PCR for FLT3-ITD was performed on genomic DNA derived from blood samples of patients before induction chemotherapy for detection of mutations. NPM1 mutation was detected in 18 patients, where 13 were type A mutants and 5 were non-type A mutants. CR, CR1-D and OS was not different according to NPM1 mutational status overall. But, non-type A NPM1 mutation was related to shorter CR1-D when compared with NPM1 wild types and NPM1 type A mutation (p = 0.004). OS was shorter in non-type A mutants when compared with NPM1 wild-type patients and NPM1 type A mutants (p = 0.001). The type of mutation of NPM1 is important for prognosis in de novo AML lacking FLT3-ITD. Non-A type NPM1 mutation is a poor prognostic factor.