| Objective: In recent years,the transplantation immunity as well as the studies on malignant blood disease were increasing,the NK cells in the process of the disease etiology,treatment and prognosis assessment research also tracked into people's vision,gained attention from the domestic and foreign scholars and clinicians.What was more important in the study of sample was a class of killer cell immunoglobulin receptor(killer cell immunoglobulin like receptor,KIR),KIR mainly existed in natural killer cells(nature killer cell)and part of the T cells on the surface of the immunoglobulin super-family member.KIR could specific identify human leukocyte antigen(human leukocyte antigen,HLA)kind of antigen system,both of which constitute the one of the most important human antigen antibody response system KIR-HLA signal system.This system once activated can control NK cells and T cell recognition foreign material of this part,and thus resulted damage function and antigen-antibody reaction.At the same time,through the study we had found that KIR also divided into two main constituent,including activated KIR and conservation of KIR,including conservation of KIR with HLA,in some of the "mismatch" background of hematopoietic stem cell transplantation,can be further enhancing driving heterologous reactivity of NK cells graft versus autoimmune reaction and promoting the role of the graft implantation in the human body.As a result,although we recognized the KIR system plays an important part in transplantation immunity,but at the same time killer cells sample immunoglobulin receptors in the human body did not underestimate the diversity of gene expression,this research focuses on exploring a certain area in Hebei province patients with hematologic malignancies genotype distribution of samples,and with the local normal crowd genotype distribution were analyzed,discussed KIR gene polymorphism and KIR genes with hematologic malignancies,the prognosis of correlation.To date,no study had been conducted on the KIR gene polymorphism and KIR genes with hematologic malignancies in Hebei.According to the domestic and foreign scholars have confirmed its exist in different RACES and different provinces and cities in south China region difference expression and clinical significance,we speculated that it may also exist polymorphism in patients with hematologic malignancies in Hebei area.The purpose of this experiment is to investigate the role of KIR in the progression of malignant leukemia disease.We collected 100 cases of patients with malignant leukemia as the experimental group of scientific research from May 2013 to May 2015 in our hospital who were laboratory confirmed,and randomly selected at the same time to the hospital for regular physical examination of 100 cases of healthy people as control group.Then we analyzes the different distribution of KIR genes,and the distribution of people with other ethnic groups or regions analysis,and follow-up in patients with hematologic malignancies,to explore the prognosis of different KIR genotypes.And further we targeted for the next step to provide theoretical basis for the clinical application of treatment for malignancies.Method:1 By using polymerase chain reaction Sequence Specific Primers(polymerase chain reaction-Sequence Specific Primers,PCR-SSP)method and KIR gene detection kits,100 cases of malignant blood disease patients and 100 cases of normal healthy check-up KIR gene polymorphism were detected to study the expression of the crowd.2 Check up the results of 100 cases of normal healthy check-up crowd in this study,we investigate the expression of KIR gene polymorphism with literature research published in the different areas and ethnic,observing the distribution of KIR genes.3 At last we used the method of single factor and multi-factors Cox regression model risk ratio method to explore the malignant blood disease of KIR gene expression and the clinical prognosis.Results:1 Basic data of cases of hematologic malignancies group and the control group We collected malignancies patients 100 cases in Hebei,male 73 cases,female 27 cases;Age 39.55±8.51;Clinical pathological classification result are as listed: the acute lymphoblastic leukemia(ALL)26 patients,24 cases of acute myeloid leukemia(AML)and acute mixed leukemia(AMLL)was 5 cases,35 cases of chronic myeloid leukemia(AML),10 cases of myelodysplastic syndrome(MDS).Normal physical examination based data derived from the same time a medical center database 100 cases of healthy normal medical personnel extracted randomly.2 Cases in hematologic malignancies and normal physical examination controls general data contrast Age distribution were 39.55±8.51 and 39.55±9.52 in hematologic malignancies group and normal physical examination control group;Sex ratio were 73.00% and 74.00% respectively;Body mass index were 25.06±3.37 and 25.06±3.21;Mental stress status,history of smoking,drinking,confidence evaluation and economic pressure condition than in the cases of hematologic malignancies was respectively: 24.00%,30.00%,10.00%,30.00% and 10.00%;Proportion in normal physical examination in the control group,respectively,29.00%,36.00%,7.00%,58.00% and 31.00%.Economic pressure cases of hematologic malignancies group was obviously higher than that of normal physical examination in the control group(P<0.05),the rest of the various social psychological factors and age,sex there were no differences of basic data,data comparable(P> 0.05).3 Cases of hematologic malignancies and normal physical examination controls KIR gene distribution and frequency contrasting Through laboratory testing,to detect the total of 16 KIR genes,the full expression of which is 3DL2,gene expression and gene frequency were reached 100.00%,the rest of KIR gene expression in the following: 3DL1(86.00%)?2DL1(95.00%)?2DL3(95.00%)?2DS4(97.00%)?2DL2(28.00%)?2DL5(34.00%)?3DS1(13.00%)?2DS1(28.00%)?2DS2(18.00%)?2DS3(15.00%)? 2DS5(31.00%)?2DL4(98.00%)?3DL2(100.00%)?3DL3(81.00%)? 2DP1(97.00%)?3DP1(79.00%)?Normal physical examination in the control group 3DP1 and 3DL3 and 2DL4,gene expression and gene frequency were reached 100.00%.Control group of KIR genes expression is as follows: 3DL1(92.00%)?2DL1(81.00%)?2DL3(99.00%)?2DS4(87.00%)?2DL2(11.00%)?2DL5(32.00%)?3DS1(28.00%)?2DS1(26.00%)?2DS2(16.00%)?2DS3(15.00%)?2DS5(25.00%)?2DL4(100.00%)?3DL2(99.00%)?3DL3(100.00%)?2DP1(95.00%)?3DP1(100.00%)?For 2DL1 ? 2DS4 and 2DL2,gene expression rate of hematologic malignancies and KIR gene,gene frequency was higher than normal physical examination control group and the difference is statistically significant(P<0.05);For 3DS1,3DL3 and 3DP1,gene expression rate of hematologic malignancies and KIR gene,gene frequencies below the normal physical examination control group and the difference was statistically significant(P < 0.05).4 Patients with hematologic malignancies and normal physical examination control KIR genotyping According to the allele frequency distribution site of KIR genotypes named,we check the analysis comparison.56 patients with hematologic malignancies has AA type,the rest 44 cases has Bx type;AA type 45 cases in normal physical examination,Bx type in 55 cases.In Hebei normal check-up crowd of KIR genotyping closest to the Japanese,AA type of relatively high,close to half level,relative to the Caucasus and African Americans are the opposite relationship.5 Through single factor analysis,compared cases in malignancies group with normal physical examination control KIR gene distribution,we finally detect the following six kinds genotype: 2DL1?2DS4?2DL2?3DS1?3DL3 and 3DP1.To include the above six genotypes in multiariable Cox regression equation,finally into the regression equation of the 2DL2 is 2 and 3DS1 two genotypes.6 2DL2 respectively 2 and 3DS1 genotype positive expression,negative expression is defined,their respective survival curve drawing respectively.Final results here genotype 2 DL2 positive expression was a risk factor for survival,and ds1 genotype 3 positive expression is the protective factors of survival time,to a log-rank test verification,the results were statistically differences(P < 0.05).Conclusion:1 Cases of hematologic malignancies and normal physical examination controls KIR gene distribution and frequency of the comparison results show that the distribution of KIR genes present differences in expression.Cases 2DL1?2DS4?2DL2,hematologic malignancies gene frequency was higher than the control group,3DS1?3DL3 and 3DP1 gene frequency was lower than the control group.2 Study in Hebei normal physical examination in the control group with other ethnic groups of normal crowd KIR genotyping situation analysis,found the Hebei KIR genes Japanese was close to normal physical examination control group,and with a greater difference between Caucasians and African Americans.Explain KIR genotyping present ethnic polymorphism quietly well.3 According to the result of multi-factors Cox regression equation of concrete and survival curve drawing,proved in this study KIR genotypes 2DL2 positive expression was a risk factor for survival,and ds1 genotype 3 positive expression is the protective factors of survival time,for the future of blood disease treatment and prognosis assessment provides some data to support. |
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