Zhu Gang-Zhi, Yang Yong-Long, Zhang Yan-Jiao, Liu Wei, Li Mu-Peng, Zeng Wen-Jing, Zhao Xie-Lan, Chen Xiao-Ping
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Haikou People's Hospital and Affiliated Haikou Hospital of Xiangya Medical School, Central South University, Haikou, China.
Cell Physiol Biochem. 2017;42(5):1973-1984. doi: 10.1159/000479837. Epub 2017 Aug 9.
BACKGROUND/AIMS: Acute myeloid leukemia (AML) is a heterogeneous clonal disease and patients with AML who harbor an FMS-like tyrosine kinase 3 (FLT3) mutation present several dilemmas for the clinician. This study aims to identify novel targets for explaining the dilemmas.
We analyzed four microarray gene expression profiles to investigate changes in whole genome expression associated with FLT3-ITD mutation.
We identified 22 differentially expressed genes which are commonly expressed among all four profiles. Kaplan-Meier analysis of the dataset GSE12417 revealed that low expression of AHSP, EPB42, GYPC and HEMGN predicted poor prognosis (AHSP: P=0.0317, HR=1.894; EPB42: P=0.0382, HR=1.859; GYPC: P=0.0015, HR=2.051; HEMGN: P=0.0418, HR=1.838 in GSE12417 test cohort; AHSP: P=0.0279, HR=1.548; EPB42: P=0.0398, HR=1.505; GYPC: P=0.0408, HR=1.501; HEMGN: P=0.0143, HR=1.630 in GSE12417 validation cohort). When patients were FLT3-ITD positive, the expression of FLT3 was significantly increased (all P<0.05 in four profiles), and correleation analysis of four profiles revealed that the expression of the four candidate genes negatively correlated with FLT3 expression.
Our findings suggest that AHSP, EPB42, GYPC and HEMGN may be suitable biomarkers for diagnostic or therapeutic strategies for FLT3-ITD-positive AML patients.
背景/目的：急性髓系白血病（AML）是一种异质性克隆性疾病，携带FMS样酪氨酸激酶3（FLT3）突变的AML患者给临床医生带来了诸多难题。本研究旨在确定解释这些难题的新靶点。
我们分析了四个微阵列基因表达谱，以研究与FLT3-ITD突变相关的全基因组表达变化。
我们鉴定出22个差异表达基因，这些基因在所有四个表达谱中均有共同表达。数据集GSE12417的Kaplan-Meier分析显示，AHSP、EPB42、GYPC和HEMGN的低表达预示着预后不良（在GSE12417测试队列中，AHSP：P = 0.0317，HR = 1.894；EPB42：P = 0.0382，HR = 1.859；GYPC：P = 0.0015，HR = 2.051；HEMGN：P = 0.0418，HR = 1.838；在GSE12417验证队列中，AHSP：P = 0.0279，HR = 1.548；EPB42：P = 0.0398，HR = 1.505；GYPC：P = 0.0408，HR = 1.501；HEMGN：P = 0.0143，HR = 1.630）。当患者FLT3-ITD呈阳性时，FLT3的表达显著增加（在四个表达谱中所有P < 0.05），并且四个表达谱的相关性分析显示，四个候选基因的表达与FLT3表达呈负相关。
我们的研究结果表明，AHSP、EPB42、GYPC和HEMGN可能是FLT3-ITD阳性AML患者诊断或治疗策略的合适生物标志物。
