摘要
背景与目的:Flt-3跨膜区内部串联重复(Flt-3internaltandemduplication,Flt-3/ITD)突变是近年来发现的Flt-3基因最常见的一种突变类型,是急性髓系白血病(acutemyeloidleukaemia,AML)中发生率最高且与预后相关的突变。本研究旨在探讨Flt-3/ITD突变与儿童白血病发生的关系及其临床意义。方法:采用聚合酶链反应(polymerasechainreaction,PCR)联合序列测定,检测302例儿童白血病患者骨髓Flt-3/ITD突变情况,其中包括AML122例、急性淋巴细胞白血病(acutelymphoblasticleukemia,ALL)124例、幼年型慢性粒细胞白血病(juvenilechronicmyelogenousleukemia,JCML)17例和骨髓异常增生综合征(myelodysplasticsyndromes,MDS)39例。结果:122例AML患者中98例(80.33%)Flt-3阳性;21例(17.21%)发生Flt-3/ITD突变,分别为M03例、M12例、M24例、M48例及M54例,突变率分别为42.86%(3/7)、22.22%(2/9)、12.90%(4/31)、44.44%(8/18)和15.38%(4/26)。此外,124例ALL中72例Flt-3阳性,阳性率为58.06%,其中2例发现Flt-3/ITD突变,突变率1.61%。测序及Blast比对分析显示,外显子11区均有ITD,各例ITD的复制区域不同,长短不等(24～95bp)。39例MDS和17例JCML患者中均未检测到Flt-3/ITD突变。临床资料显示,21例Flt-3/ITD突变的AML患者中有19例在短期内死亡,这19例的中位生存时间为13.5个月(0～47个月),死亡率为90.48%,与无Flt-3/ITD突变患者相比有显著性差异(P<0.05)。Flt-3/ITD突变阳性患者外周血中性粒细胞平均比率与Flt-3/ITD突变阴性患者无显著性差异(P>0.05)。染色体核型分析显示,Flt-3/ITD的AML患者中3例存在有染色体异位,分别为t(11;12)(p15;q13)、t(6;9)(p23;q23)、inv16(q21;q23)。结论:Flt-3/ITD突变多发现于AML,罕见于ALL,未见于MDS和JCML。该突变与儿童白血病特别是儿童AML的发生及进展有关。Flt-3/ITD可以作为判断AML预后的重要标志之一。
BACKGROUND ＆ OBJECTIVE： Flt-3 internal tandem duplication （Flt-3/ITD） in transmembrane region is the most frequently identified mutation in Flt-3 gene, which is the most frequently happened in acute myeloid leukemia （AML） and correlated to prognosis. This study was to explore the correlation of Flt-3/ITD mutation to the occurrence of pediatric leukemia, and analyze its clinical significance. METHODS. Flt-3/ITD mutation status in bone marrow samples from 302 children with leukemia, including 122 cases of AML, 124 cases of acute lymphoblastic leukemia （ALL）, 17 cases of juvenile chronic myelogenous leukemia （JCML）, and 39 cases of myelodysplastic syndromes （MDS）, were examined by polymerase chain reaction （PCR） and sequencing. RESULTS, Of the 122 AML patients, 98 （80.32%） had Flt-3 gene products in bone marrow. Flt-3/ITD mutation was detected in 21 （17.21%） of the 122 patients; the mutation rates were 42.86% （3/7） in M0, 22.22% （2/9） in M1, 12.90% （4/31） in M2, 44.44% （8/18） in M4, and 15.38% （4/26） in M5. Of the 124 ALL patients, 72 （58.06%） had Flt-3 gene products in bone marrow. Flt-3/ITD mutation was found in 2 （1.61%） of the 72 patients. DNA sequencing and Blast alignment revealed that ITD within exon 11 existed in all samples, with various duplication regions and lengths （24-95 bp）. No Flt-3/ITD mutation was found in MDS patients and JCML patients. Of the 19 AML patients with Flt3/ ITD mutation, the median survival time was 13.5 months （0-47 months）, which was significantly shorter than that of the patients without Flt-3/ITD mutation （P〈0.05）. The percentage of neutrophils in peripheral blood was similar in Flt-3/ITD-positive and Flt-3/ITD-negative patients （P〉0.05）. Chromosome karyotype analysis showed chromosome abnormity, including t （11;12）（p15;q13）, inv16（q21;q23）, and t（6;9）（p23;q23）, in 3 AML patients with Flt-3/ITD. CONCLUSIONS： Flt-3/ITD mutations are usually detected in AML, seldom in ALL, not in MDS and JCML. Flt-3/ITD mutation is correlated to AML onset and progress. Flt-3/ITD is a significant marker to analyze AML prognosis.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2007年第1期58-63,共6页
Chinese Journal of Cancer
