目的：探讨FMS样酪氨酸激酶3(FLT3)基因的内部串联复制（ITD）及激酶结构域（TKD）点突变在儿童急性髓系白血病（AML）中的临床意义。方法：通过实时定量PCR法对116名初诊AML儿童进行骨髓FLT3/ITD及FLT3/TKD突变检测，分析FLT3/ITD及FLT3/TKD突变与AML临床特征、疗效之间的关系。结果：116名患儿中，伴有FLT3/ITD及FLT3/TKD突变分别为9例（7.8%）、13例（11.2%）。3例AML-M3(3/9,33.3%)及3例AML-M5(3/9,33.3%)患儿出现FLT3/ITD突变；FLT3/TKD突变以AML-M3最多见（10/13，76.9%）。伴FLT3/ITD突变患儿较不伴该突变的患儿初诊时具有更高的白细胞及骨髓幼稚细胞比例（P<0.01）。伴FLT3/ITD突变患儿3年总生存率明显低于不伴该突变患儿（38.9% vs 64.3%，P<0.05）。结论：FLT3/TKD突变多见于儿童AML-M3患者；伴FLT3/ITD突变患儿初诊时具有更高的白细胞及骨髓幼稚细胞比例，且预后更差。
Abstract
OBJECTIVE: To study the clinical significance of FMS-like tyrosine kinase 3 (FLT3) mutations including internal tandem duplication (ITD) mutation and point mutation of tyrosine kinase domain (TKD) in children with acute myeloid leukemia (AML). METHODS: Bone marrow samples from 116 children with newly-diagnosed AML were obtained．Gene mutations of FLT3/ITD and FLT3/TKD were detected by RT-PCR. The relationship of FLT3 gene mutations with the clinical characteristics and the therapeutic efficacy was observed. RESULTS: FLT3/ITD and FLT3/TKD mutations were detected in 9 cases (7.8%) and 13 cases (11.2%) respectively out of the 116 children. FLT3/ITD mutations were observed in 3 cases of AML-M3 (3/9; 33.3%) and in 3 cases of AML-M5 (3/9; 33.3%). FLT3/TKD mutations were the most common in AML-M3 patients (10/13; 76.9%). The patients with FLT3/ITD mutations had a significantly higher peripheral WBC count and marrow blast percentage compared with the patients without FLT3/ITD mutations at diagnosis (P<0.01). The 3-year overall survival rate in patients with FLT3/ITD mutations was significantly lower than that in patients without FLT3/ITD mutations (38.9% vs 64.3%; P<0.05).ConclusionsFLT3/TKD mutations are common in children with AML-M3. The AML children with FLT3/ITD mutations present a high peripheral WBC count and a high marrow blast percentage at diagnosis and have an unfavorable outcome.
关键词
急性髓系白血病 /
FLT3 /
基因突变 /
儿童
Key words
Acute myeloid leukemia /
FLT3 /
Gene mutation /
Child
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