老年急性髓细胞白血病患者FLT3-ITD基因突变的临床意义

Prevalence and clinical significance of FLT3 internal tandem duplication mutation in acute myeloid leukemia of older people

目的分析老年急性髓细胞白血病（AML）Fms样酪氨酸激酶3内部串联重复序列（FLT3-ITD）基因突变及其临床意义。方法采用聚合酶链反应-变性高效液相色谱技术（PCR—DHPLC）分析30例初发老年AML患者骨髓单个核细胞FLT3-ITD突变。结果30例老年AML患者FLT3-ITD突变阳性率26．67％（8／30），对照组均未检测到该突变；FAB各亚型FLT3-ITD突变率不同，有M，型突变率较高的趋势；所检测到FLT3-ITD突变均为杂合突变，突变均在阅读框内；不同预后核型组FLT3-ITD突变阳性率不同，预后中等核型组突变率较高，达40．0％（6／15）；显示FLT3-ITD突变阳性者具有高白细胞、白血病细胞、完全缓解（CR）率低等临床特点。结论FLT3—1TD突变阳性老年AML患者预后差，且多发生于预后中等核型组；FLT3-ITD突变检测在-定程度上可以弥补细胞遗传学的不足，有可能成为老年AML患者常规检测项目，以指导治疗判断预后。

Objective The aim of the study was to detect the mutation of Fms-like tyrosine kinase 3 internal tandem duplication （FLT3-ITD） rate in older de novo acute myeloid leukemia （AML） patients, to evaluate the role of FLT3-ITD in AML and its clinical significance. Methods The mutations of FLT3-1TD in hone marrow mononuclear cells （MNCS） from 30 cases of older AML were screened by polymerase chain reaction denaturing-high performance liquid chromatography （PCR-DHPLC）. Results FLT3-ITD mutations were identified in 26.67 %（8/30） patients, while there were no mutations identified in control cases. And these kinds of mutations were likely to attend in Ms types. All mutations of FLT3-ITD were heterozygous and rearrangement fragment located in reading frame. Different karyomite groups had different FLT3-ITD mutations rate. We could see that FLT3-ITD positive patients were more prevalent in patients with normal karyotype. Clinical researches indicated that FLT3-ITD mutations had the characteristics of a higher peripheral white cell count, higher blast cells and lower complete remission rate in older AML Conclusion FLT3-ITD positive older AML patients conferred a poor prognosis and were likely to attend in normal karyomite group. The detection of FLT3-ITD mutations could make up for the deficiency of cytogenetics to some extent, and may become a routine examination of AML in older, which can direct their treatment and predict their prognosis.