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本研究探讨急性髓系白血病(acute myeloid leukemia,AML)患者中FMS样酪氨酸激酶3(FLT3)基因内部串联重复突变(ITD)及第二酪氨酸激酶结构域(TKD)点突变及其临床意义。采用基因组DNA-PCR方法检测131例初发AML患者骨髓单个核细胞FLT3基因外显子14、15中ITD突变,采用基因组DNA-PCR结合限制性内切酶酶切方法检测FLT3基因外显子20中TKD点突变。结果表明:131例初治AML患者中,21例(16.0%)FLT3-ITD突变阳性,3例(2.3%)FLT3-TKD点突变阳性,无同一患者同时发生两种突变。FLT3-ITD阳性组初诊时白细胞计数(WBC)及骨髓原始细胞比例高于野生型FLT3(FLT3-wt)组。FLT3-ITD阳性组患者完全缓解(CR)率47.6%,显著低于FLT3-wt88.1%(p<0.05)。20例M3患者中,FLT3-ITD阳性组及阴性组患者缓解率差异无统计学意义;非M3FLT3-ITD阳性组患者CR率为37.5(6/16例),显著低于非M3FLT3-wt组患者CR率90.6%(48/53例)(p<0.05)。阳性组患者完全缓解后14个月(2-20个月)内复发3例,复发率为50%(3/6),高于FLT3-wt组29.2%(14/48例)。由于FLT3-TKD阳性患者仅3例,未单独进行统计学分析。结论:FLT3基因突变是AML患者中常见的突变,FLT3-ITD突变较FLT3-TKD点突变发生率高,FLT3-ITD有突变的AML患者预后差;FLT3-TKD点突变对预后的影响不明显。临床上早期FLT3基因突变检测对AML患者今后的靶向治疗及了解临床预后有重要意义。
This study was designed to investigate the point mutations of the ITM and the second tyrosine kinase domain (TKD) in the FMS-like tyrosine kinase 3 (FLT3) gene in patients with acute myeloid leukemia (AML) Clinical significance. Genomic DNA-PCR was used to detect ITD mutations in exon 14 and 15 of FLT3 gene in 131 cases with primary AML. Genomic DNA-PCR and restriction enzyme digestion were used to detect FLT3 exon 20 In TKD point mutation. The results showed that FLT3-ITD mutation was positive in 21 cases (16.0%) and FLT3-TKD mutation in 3 cases (2.3%) in 131 cases of newly diagnosed AML patients. No mutation occurred in the same patient. The number of white blood cell count (WBC) and bone marrow blasts in FLT3-ITD positive group was higher than that in wild type FLT3-wt group. Patients in the FLT3-ITD positive group had a complete remission (CR) rate of 47.6%, significantly lower than FLT3-wt88.1% (p <0.05). Among 20 patients with M3, the response rate of FLT3-ITD positive group and negative group was no significant difference. The CR rate of non-M3FLT3-ITD positive group was 37.5 (6/16 cases), which was significantly lower than that of non-M3FLT3-ITD group The CR rate was 90.6% (48/53 cases) (p <0.05). In the positive group, 3 cases relapsed within 14 months (2-20 months) after complete remission, the recurrence rate was 50% (3/6), which was higher than that in FLT3-wt group (29.2%, 14/48 cases). Since only 3 patients were positive for FLT3-TKD, no statistical analysis was performed separately. CONCLUSIONS: FLT3 gene mutation is a common mutation in AML patients. FLT3-ITD mutation has a higher incidence of point mutations than FLT3-TKD, and patients with FLT3-ITD mutations have a poor prognosis. FLT3-TKD mutation has no obvious effect on prognosis. Clinical detection of early FLT3 gene mutation in patients with AML in the future targeted therapy and to understand the clinical prognosis of great significance.