急性髓系白血病Kindlins和血管生成素表达研究

本研究旨在探讨不同白血病细胞系、成人急性髓系白血病Ang-1、Ang-2、Tie-2、Kindlin-2、Kindlin-3的表达情况及其意义。采用RQ-PCR方法检测88例AML患者、9例非肿瘤患者(对照组)以及K562、KG-1a、U937、HL-60、Jurkat细胞株中Ang-1、Ang-2、Tie-2、Kindlin-2、Kindlin-3表达水平,分析阳性率及表达水平在AML患者与对照组间的差异,探讨上述5种基因之间及其与AML分型、预后的关系。结果表明,Ang-1,Ang-2,Kindlin-3在K562、KG-1a、HL-60、U937、Jurkat细胞系中均有表达,Tie-2仅表达于KG-1a、HL-60细胞系中,Kindlin-2表达于K562、KG-1a、HL-60中。5种基因均表达于AML患者及对照组中。Ang-1、Ang-2在起病时白细胞计数较高组的表达水平较高(P<0.001,P=0.001),在伴有t(8;21)和t(15;17)的AML患者中表达均较低(P<0.001,P=0.005)。Ang-1在NCCN预后良好组表达较低(P=0.020);Ang-1低表达组完全缓解率(CR)较高(P=0.027)。Kindlin-2在AML患者中表达水平较低(P=0.010),起病时白细胞计数较高组的表达水平较低(P=0.020),伴有t(8;21)和t(15;17)AML的表达均较高(P=0.016),治疗缓解后Kindlin-2及Kindlin-3表达明显升高(P<0.001,P=0.004)。结论:Ang-1与AML不良预后因素相关;Kindlin-2在AML中低表达,与AML良好预后因素相关,可能是一个预后较好的标志。

Expression of Kindlins and angiopoietins in acute myeloid leukemia

This study was purposed to explore the expression of Ang-1, Ang-2, Tie-2, Kindlin-2, Kindlin-3 in different leukemia cell lines and bone marrow of acute myeloid leukemia (AML) patients and its clinical significance. The levels of Ang-1, Ang-2, Tie-2, Kindlin-2, Kindlin-3 in bone marrow of AML patients and nontumorous control group as well as leukemia cell lines (K562, KG-1a, U937, HL-60 and Jurkat) were detected by RQ-PCR. The difference of positive rate and expression level between AML patients and controls was analyzed. The relation between 5 genes and their relationship with typing and prognosis of AML were investigated. The results showed that Ang-1, Ang-2, Kindlin-3 expressed in K562, KG-1a, U937, HL-60 and Jurkat cells. Tie-2 only expressed in KG-1a and HL-60 cells. Kindlin-2 expressed in K562, KG-1a and HL-60 cells. All of these 5 genes expressed in AML patients and nontumorous controls. The expression level of Ang-1 and Ang-2 in patients with higher WBC count (≥ 30 × 10(9)/L) was significantly higher than that in patients with lower WBC (< 30 × 10(9)/L, P < 0.001, P < 0.001). The expression level of Ang-1 and Ang-2 in patients with t(8;21) or t(15;17) was significantly lower (P < 0.001, P = 0.005). In the NCCN better-risk group, Ang-1 expressed lower (P = 0.020). The group with lower expression of Ang-1 showed a higher complete remission (CR) rate (P = 0.027). The expression level of Kindlin-2 was lower in AML patients (P = 0.010), lower in patients with higher WBC (≥ 30 × 10(9)/L, P = 0.020), and higher in patients with t(8;21) or t(15;17). The expression levels of both Kindlin-2 and Kindlin-3 were significantly higher after CR (P < 0.001, P = 0.004). It is concluded that Ang-1 closely correlated with the poor prognosis of AML. Kindlin-2 lowly expresses in AML, which has a close relation with the favorable prognosis of AML. Kindlin-2 can be a marker for favorable prognosis of AML.