中期因子在急性髓系白血病患者的表达及临床意义

为了探讨中期因子(midkine,MK)与急性髓系白血病(AML)患者预后的关系,本研究采用半定量RT-PCR方法检测65例AML患者与15例正常人骨髓单个核细胞(MNC)MK、bcl-2mRNA的表达,并对20例AML患者和5例正常人采用Westernblot检测MNC中MK基因的表达。结果显示:初治组、复发组和化疗缓解组MK基因表达水平分别为0.331±0.436,0.374±0.463和0.067±0.190,正常人MK基因表达阴性;MK基因表达阳性与表达阴性患者的首次完全缓解(CR)率分别为63.16%和93.55%(P=0.01),MK基因表达阳性患者的复发率(100%)明显高于表达阴性者(40%)(P=0.019);多药耐药组与药物敏感组MK基因的表达率分别为57.69%和25.64%(P<0.01);MK与bcl-2基因表达呈正相关(r=0.556,P<0.001)。结论:AML患者白血病细胞可以产生MK,且MK阳性率的高低与AML病期相关,是影响AML患者近期预后的重要因素之一。MK可能通过上调bcl-2的表达抑制白血病细胞凋亡。

Expression of Midkine in Patients with Acute Myeloid Leukemia and Its Significance

The study was aimed to investigate the expression of midkine (MK) in bone marrow mononuclear cells (BM MNC) from 65 acute myeloid leukemia patients and 15 normal controls. The method of RT-PCR was used to examine the expression of MK mRNA in BM MNC. Parts of samples were incubated for 24 hours and the gene expression of MK in the BM MNC was detected by means of Western blot. The results showed that the expression of MK of BM MNCs in 50 newly diagnosed AML patients (0.331 +/- 0.436) and 15 AML patients in relapse (0.374 +/- 0.463) were markedly higher than that in 15 CR cases (0.067 +/- 0.190), and 15 normal controls (0), respectively. The complete remission in MK positive patients (63.16%) was significantly lower than that in MK negative group (93.55%). The patients with positive MK expression had a higher relapse rate than those with negative MK expression. The positive rate of MK gene expression in drug-resistant patients and drug-sensitive patients were 57.69% and 25.64% respectively and there was positive correlation between the gene expressions of MK and bcl-2 (P < 0.01) (r = 0.0556, P < 0.001). It is concluded that MK can be secreted by AML cells and involved in drug-resistant, its positive expression may be associated with the poor prognosis in newly diagnosed AML patients. The inhibitory effect of MK on apoptosis of leukemic cells is induced by upregulating bcl-2 expression.