Department of Hematology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
J Zhejiang Univ Sci B. 2010 Oct;11(10):762-70. doi: 10.1631/jzus.B1000052.
Mutations of fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) exon 12 genes are the most common abnormalities in adult acute myeloid leukemia (AML) with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction (PCR) and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication (FLT3/ITD) and exon 12 of the NPM1 gene. FLT3/ITD mutation was detected in 15 (19.7%) of 76 subjects, and NPM1 mutation in 20 (26.3%) subjects. Seven (9.2%) cases were positive for both FLT3/ITD and NPM1 mutations. Significantly more FLT3/ITD aberration was detected in subjects with French-American-British (FAB) M1 (42.8%). NPM1 mutation was frequently detected in subjects with M5 (47.1%) and infrequently in subjects with M2 (11.1%). FLT3 and NPM1 mutations were significantly associated with a higher white blood cell count in peripheral blood and a lower CD34 antigen expression, but not age, sex, or platelet count. Statistical analysis revealed that the FLT3/ITD-positive group had a lower complete remission (CR) rate (53.3% vs. 83.6%). Survival analysis showed that the FLT3/ITD-positive/NPM1 mutation-negative group had worse overall survival (OS) and relapse-free survival (RFS). The FLT3/ITD-positive/NPM1 mutation-positive group showed a trend towards favorable survival compared with the FLT3/ITD-positive/NPM1 mutation-negative group (P=0.069). Our results indicate that the FLT3/ITD mutation might be a prognostic factor for an unfavorable outcome in Chinese AML subjects with normal cytogenetics, while NPM1 mutation may be a favorable prognostic factor for OS and RFS in the presence of FLT3/ITD.
Fms 样酪氨酸激酶 3（FLT3）和核磷蛋白（NPM1）外显子 12 基因突变是正常细胞遗传学成人急性髓细胞白血病（AML）中最常见的异常。为了评估这两种基因突变在中国 AML 患者中的预后影响，我们使用多重聚合酶链反应（PCR）和毛细管电泳技术筛查了 76 例正常细胞遗传学 AML 患者的 FLT3 内部串联重复（FLT3/ITD）和 NPM1 基因外显子 12 的突变。在 76 名受试者中，检测到 FLT3/ITD 突变 15 例（19.7%），NPM1 突变 20 例（26.3%）。7 例（9.2%）患者同时存在 FLT3/ITD 和 NPM1 突变。FAB M1（42.8%）患者中更常检测到 FLT3/ITD 异常。NPM1 突变在 M5（47.1%）患者中较常见，在 M2（11.1%）患者中较少见。FLT3 和 NPM1 突变与外周血白细胞计数较高和 CD34 抗原表达较低显著相关，但与年龄、性别或血小板计数无关。统计分析显示，FLT3/ITD 阳性组完全缓解（CR）率较低（53.3% vs. 83.6%）。生存分析显示，FLT3/ITD 阳性/NPM1 突变阴性组的总生存（OS）和无复发生存（RFS）较差。与 FLT3/ITD 阳性/NPM1 突变阴性组相比，FLT3/ITD 阳性/NPM1 突变阳性组的生存情况较好（P=0.069）。我们的结果表明，FLT3/ITD 突变可能是中国正常细胞遗传学 AML 患者不良预后的一个预测因素，而 NPM1 突变可能是存在 FLT3/ITD 时 OS 和 RFS 的一个有利预后因素。
