几类恶性血液病病人杀伤免疫球蛋白样受体基因型的表达在高危及标危组的差异分析

Differential Expression Levels of Killer Immunoglobin-like Receptor Genotype in Patients with Hematological Malignancies between High-risk and Standard-risk Groups

本研究探讨几类高危和标危恶性血液病患者杀伤免疫球蛋白样受体(KIR)基因表达的异同。54例恶性血液病患者分为高危组(27例)和低危组(27例),其中急性髓系白血病14例、急性淋巴细胞白血病16例、慢性髓系白血病20例、骨髓增生异常综合征3例、急性混合白血病1例。用序列特异性引物PCR分型技术检测了6个激活性KIR基因(KIR2DS1-S5、3DS1)和6个抑制性KIR基因(KIR2DL1-2DL4、3DL1-3DL2)的表达,其中24例患者用流式细胞仪测定了NK细胞、T细胞表面CD158a(KIR2DL1、2DS1)、CD158b(KIR2DL2、2DL3、2DS2、2DS3)、CD158e(KIR3DL1、3DS1)的表达。结果显示,标危组病人激活性KIR基因的阳性率均高于高危组患者,2DS1(p=0.014)、2DS2(p=0.046)、3DS1(p=0.005)的差异有统计学意义;抑制性KIR基因的表达在两组患者之间的差异无统计学意义(p>0.05)。在髓系恶性血液病病人中标危组病人KIR激活性基因表达率仍然高于高危组患者,其中2DS1(66.7%vs29.4%,p=0.022)、2DS2(57.6%vs17.6%,p=0.013)和2DS3(33.3%vs5.9%,p=0.039)。高危组患者同时表达两种以上激活性KIR基因的比例显著低于标危组(p=0.035)。高危和标危组患者NK细胞和T细胞表面CD158a、CD158b、CD158e的表达差异无统计学意义(p>0.05)。结论:几类恶性血液病患者激活性KIR基因表达在高危和标危之间存在差异。

This study was purposed to investigate the killer immunoglobulin-like receptor （KIR） genotype in patients with hematological malignancies. The sequence specific primer-polymerase chain reaction （PCR-SSP） technique was performed for the amplification of six inhibitory KIR genes （KIR2DL1-2DL4,3DL1-3DL2） and six activating KIR genes （KIR2DS1-S5,3DS1）. The methods of KIR-SSP was used to deterrmine the KIR genotypes of 54 leukemia patients, including 14 patients with acute myeloid leukemia （AML）, 16 with acute lymphoblastic leukemia （ALL）, 20 with chronic myeloid leukemia （CML）, 3 with myelodysplastic syndrome （MDS） and 1 with acute myeloid-lymphoblast leukemia （AMLL）. 54 patients were classified as high risk group （n =27） and standard risk group （n = 27）. The expression of KIR in NK cells and T cells was detected by flow cytometry. The frequencies of activating KIR genes in standard risk group were higher than those in high risk group, especially 2DS1 （p =0.014）, or 2DS2 （p =0.046）, or 3DS1 （p =0.027）. However, the frequencies of inhibitory KIR genes in standard risk group were similar to those in high risk group （p 〉0.05）. The frequencies of activating KIR genes were also higher in standard risk patients with acute AML, as compared with those in high risk patients with acute AML, particularly 2DS1 （66. 7% vs 29.4%, p =0. 022）, 2DS2 （57. 6% vs 17.6%, p =0. 013）, and 2DS3 （33.3% vs 5.9%, p =0. 039）. The percentages of patients in high- risk group who expressed more than two kinds of activating KIRs were lower that those in standard-risk group （p =0.035）. There was no difference in the expressions of CD158a, CD158b, and CD158e on NK cells and T cells between high-risk group and standard-risk group （p 〉0.05）. In conclusions, different expressions of activating KIR genes were found in patients between high- risk group and standard-risk group.