急性非淋巴细胞白血病患者c-kit受体表达及其功能的研究

c-kit receptor expression and its function in acute nonlymphoblastic leukemia

目的：研究c-kit受体(c-kit receptor,c-kit R)在急性白血病(acute leukemia,AL)的表达,探讨c-kit R的功能是否异常。方法：运用流式细胞术(flow cytometry,FCM)分别检测92倒急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)和81例急性非淋巴细胞白血病(acute nonlymphoblastic leukemia,ANLL)患者骨髓单核细胞(bone marrow mononuclear cell,BMMNC)跨膜c-kit R表达的阳性率和阳性水平；采用干细胞因子(stem cell factor,SCF)、重组人白介素3(recombinant hu- man interIeukin-3,rhIL-3)和重组人红细胞生成素(recombinant human erythropoietin,rhEPO)三种造血生长因子(hematopoi- etic growth factor,HGF)共培养4例正常人和8例ANLL组患者BMMNC,二组分别设HGFs培养前的标本为对照组,运用FCM分别检测正常人和ANLL二组的对照组以及HGFs培养后第4、8和12小时3个时间点的c-kit R阳性率和阳性水平。结果：①ANLL组患者c-kit R表达的阳性率及阳性水平均值分别为71.6%和(45.3±16.50)%,均明显高于正常人和ALL组患者(P值分别＜0.001)；②4例正常人对照组(HGFs培养前)的c-kit R阳性水平均值为(3.90±0.99)%；HGFs培养后第4、8和第12小时的c-kit R阳性水平分别为(5.8±4.05)%,(7.3±6.10)%和(8.3±5.20)%,与对照组之间无统计学意义的差异(P＞0.05),8例ANLL对照组(HGFs培养前)的c-kit R阳性水平的均值为(45.6±15.08)%,HGFs培养后三个时间点的c-kit R阳性水平的均值分别为(6.1±2.78)%、(5.8±2.58)%和(5.5±2.48)%,都低于对照组(P分别＜0.001),c-kit表达呈总体下调趋势。结论：c-kit R可作为AL的髓系免疫学标志物；HGFs对ANLL患者c-kit R的调控异常,提示在ANLL高表达的c-kit R的功能异常。

Objective：To explore the expression of c-kit receptor in the patients with acute nonlymphoblastic leukemia （ANLL） and further determine whether it has normal function. Methods：Flow cytometry analysis （FCM） was used to detect the positive rate and positive level of transmembrane c-kit receptor expression in bone marrow mononuclear cells from 92 patients with acute lymphoblastic leukemia （ALL） and 81 patients with ANLL. Bone marrow mononuclear cells from 4 healthy controls and 8 ANLL patients were co-cultured with three hematopoietic growth factors （HGF）. They are stem cell factor （SCF）, recombinant human interleukin-3 （rhIL-3）, and recombinant human erythropoietin （rhEPO）. The positive level of c-kit receptor before and at 4, 8, and 12 h after co-culture with HGF were detected by FCM. Results：①The positive rate and average positive level of c-kit receptor expression in 81 patients with ANLL was 71.6% and （45.3±16.5）%, respectively, higher than those in healthy controis and patients with ALL （all P〈0.001）. ②The average positive level of c-kit receptor expression in 4 healthy controls before HGFs co-culture was （3. 90±0.99）%, which had no significant difference with those measured at 4, 8, and 12 h after HGFs co-culture（P=0. 185）. The average positive level of e-kit receptor expression in 8 ANLL patients before HGFs co-culture was （45.6±15.08）% . The expressions of c-kit receptor were at 4, 8, and 12 h after HGFs co-culture were （6.10±2.78）%, （5.80±2.58）%, and（5.50±2.48）% , respectively, which were all significanty lower than control group （all P〈0.001 ）. It was down-regulated gradually. Conclusion：The c-kit receptor has the potential to be the myeloid immunological marker for acute leukemia. The abnormal regulation of c-kit receptor by HGFs suggests that c-kit receptor highly expresses in ANLL patients that has abnormal function.