Wang Jie, Li Shu, Wang Tong
Department of Biochemistry and Molecular Biology, Shenyang Medical College, Shenyang 110034, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Aug;15(4):700-4.
This study was to explore the clinical significance of FLT3 internal tandem duplication (FLT3/ITD) in acute myeloid leukemia (AML) with chromosome abnormality. Karyotypes in 125 AML patients were analyzed by R banding technique. Using genomic PCR and sequencing, FLT3/ITD mutation in AML patients with or without chromosome abnormity were examined. The results indicated that chromosome abnormality with various types was found in 46 out of 125 samples, the positive rate was 36.8%. The positive rate in different chromosome subtypes included M(0) 57.14%, M(1) 55.56%, M(2) 38.71%, M(3) 50.0%, M(4) 50.0%, M(5) 30.77%, M(6)/M(7) 10.0% and M(7) 18.75% respectively. In various chromosome abnormality types, t (16, 21) occurred in 9 samples with highest rate 19.78%, and the others were t (8, 21) in 7 samples, t (4, 11) in 6 samples with the occurrence rate 15.22%, 13.04% respectively. Besides, t (6, 9) was detected in 3 samples which was seldom found domestically, the positive rate was 6.52%. In 79 samples without chromosome abnormality, FLT3 gene expression was detected in 56 samples, the positive rate was 70.89%. In 46 samples with chromosome translocation, FLT3 gene expression could be detected in 31 samples, the positive rate was 67.39%. The difference between them was no significant (p > 0.05). And the FLT3/ITD mutation rates in these two groups were 11.39% and 24.09% respectively, whose difference was statistically significant (p < 0.05). Clinical data showed that the difference was no statistically significant (p > 0.05) in leukocyte counting and Hb assay in peripheral blood as well as leukocyte ratio in bone marrow of these two groups with or without chromosome abnormality. Most FLT3/ITD mutation patients with or without chromosome abnormality died in short time, the difference of death rate was not statistically significant between these two groups (p > 0.05) while the life span of FLT3/ITD mutation patients with chromosome abnormality was even shorter than the other. The difference between them was statistically significant (p < 0.05). It is concluded that prognosis is relatively poor in FLT3/ITD mutation patients with chromosome abnormality. FLT3/ITD mutation may be an important marker for poor prognosis of AML.
本研究旨在探讨FMS样酪氨酸激酶3内部串联重复(FLT3/ITD)在伴有染色体异常的急性髓系白血病(AML)中的临床意义。采用R显带技术分析125例AML患者的核型。运用基因组PCR和测序技术,检测伴有或不伴有染色体异常的AML患者的FLT3/ITD突变情况。结果显示,125份样本中有46份存在不同类型的染色体异常,阳性率为36.8%。不同染色体亚型的阳性率分别为:M(0) 57.14%、M(1) 55.56%、M(2) 38.71%、M(3) 50.0%、M(4) 50.0%、M(5) 30.77%、M(6)/M(7) 10.0%以及M(7) 18.75%。在各种染色体异常类型中,9份样本出现t(16, 21),发生率最高,为19.78%;其他依次为7份样本出现t(8, 21),6份样本出现t(4, 11),发生率分别为15.22%、13.04%。此外,3份样本检测到t(6, 9),在国内较少见,阳性率为6.52%。在79份无染色体异常的样本中,56份检测到FLT3基因表达,阳性率为70.89%。在46份有染色体易位的样本中,31份可检测到FLT3基因表达,阳性率为67.39%。两者差异无统计学意义(p>0.05)。这两组的FLT3/ITD突变率分别为11.39%和24.09%,差异具有统计学意义(p<0.05)。临床资料显示,伴有或不伴有染色体异常的这两组患者在外周血白细胞计数、血红蛋白检测以及骨髓白细胞比例方面差异无统计学意义(p>0.05)。大多数伴有或不伴有染色体异常的FLT3/ITD突变患者在短期内死亡,两组死亡率差异无统计学意义(p>0.05),但伴有染色体异常的FLT3/ITD突变患者的生存期甚至更短。两者差异具有统计学意义(p<0.05)。结论是,伴有染色体异常的FLT3/ITD突变患者预后相对较差。FLT3/ITD突变可能是AML预后不良的一个重要标志物。