To Discuss The Expression Level And Clinical Significance In Unrelated Allogeneic Hematopoietic SCT

【Objectives】The protein expression level of KIR3DL1 in patient with hematologic malignancies at the first visit,the healthy donors,patient received unrelated allogeneic hematopoietic stem-cell transplantation was analyzed in this paper,also KIR gene-type,haplo-type were analyzed,and we,and we Analysis of the KIR gene-type,haplo-type and expression levelof KIR 3DL1 about healthy donors from the angle of KIR/HLA receptor-ligand model,provide more comprehensive and scientific experiment data for impact of KIR3DL1 in unrelated allogeneic hematopoietic stem-cell transplantation【Methods】A total of 116 cases of patients received unrealted hematopoietic stem cell transplantation(include 60 cases of AML and MDS、40 cases of ALL、8 cases of CML and 6 cases of other malignant hemoblastosis), 92 cases of healthy donors and 20 cases of malignant hemoblastosis patient at first visit,all of they were performed KIR genotyping,HLA high-resoluction typing,KIR3DL1 expression level using PCR-SSP,sequence-based testing(SBT) and flow cytometry methods, KIR gene-type,haplo-type were analyzed,studied the inhibitory KIR3DL1 expression from the angle of KIR/HLA receptor-ligand model;KIR genotyping,KIR3DL1 expression level,analysis KIR3DL1 expression level difference between the first visit patients and healthy donor,KIR3DL1 reconstruction after transplantation. At the same time, combined with clinical data analysis after transplantation,research expression level of KIR3DL1 in immune tolerance group, a GVHD group and relapse group【Results】PART I Analysis of the KIR gene-type,haplo-type and expression levelof KIR 3DL1 about healthy donors1) in 92 healthy donors, KIR-AA, Bx1, Bx2 for common genotypes, frequency were 46.8%(43/92),18.5%(17/92) and 10.2%(9/92);KIR-A,B1,B2,B3,B4 for common KIR haploid type,frequency were 69%(128/182),11%(20/182),7%(13/182), 5%(8/182),1%(2/182).2) KIR3DL1 genes identified donor recipients of HLA-BW4 ligand,in 92 cases of donor the frequency of HLA- BW4 / BW4, HLA- BW4 / BW6,BW6 / BW6 ligands are 13.79%, 67.81% and 13.79% respectively, the difference between distribution(P < 0.0001).3) KIR3DL1 expression level Haplo-type KIR- A/A and KIR- B/x, KIR- B/B are 18.77%, 13.14% and 0.37% respectively, show statistically significant, P value is 0.039, 0.0003, 0.0003 respectively.In haploid KIR- B/x at the same time express KIR3DL1/2Dl2 and no 2DL2 KIR3DL1 genes expression levels were 16.3% and 11.2% respectively, show no statistical differences.But KIR3DL1 expression level in haploid type KIR- A/A and haploid KIR- B/x 2DL2 genes,Compared two groups was statistically differencewas statistically significant(p = 0.019).4) KIR3DL1 recognition group(HLA-BW4 positive group) expression level is higher than KIR3DL1 don’t recognize group(HLA- BW4 negative group),are 17.61% and 10.65% respectively, compared two groups was statistically difference(p = 0.006). PART II Analysis of the KIR3DL1 expression and clinical significance in unrealted hematopoietic stem cell transplantation.1)KIR3DL1 expression level of KIR-AA genetype in healthy donors and patients at first visit are 20.39% and 9.7% respectively,KIR3DL1 expression level of KIR-Bx genetype in healthy donors and patients at first visit are 15.94% and 6.8% respectively(p=0.038,p=0.023)2) In the immune tolerance group, KIR3DL1 expression level was 27.74%、23.56%、26.61% respectively at the first month,the second month,the third month,when compared with donors,there was no statistically difference(p>0.05),KIR3DL1 expression level in recognition group was higher than not recognition group after transplantation,was 21.86% and 16.54% respectively(p=0.046) at the first month, was 19.51% and 16.54% respectively at the second month(p=0.27), was 19.19% and 10.86% respectively(p=0.014)。3) KIR3DL1 expression level of Donor for KIR- AA genotype in relapse group after transplantation were lower than that of immune tolerance group, expression level of 19.11% in the first month, compared with the immune tolerance groups was statistically difference(p = 0.023), and expression level at 2,3 month was low, were 19.84% and 13.69%, respectively, compared with the immune tolerance group no statistical difference.Donor for KIR- Bx genotype KIR3DL1 expression levels in recurrent group were lower than that the immune tolerance, but did not show statistically significant.At the same time when the immune tolerance group and recurrence group are KIR3DL1 identify HLA- BW4 recurrence KIR3DL1 expression level is lower than the immune tolerance group, but no significant statistical difference.4) When the donor KIR3DL1 don’t identify HLA-BW6/BW6 ligand, in a GVHD group KIR3DL1 expression level was higher than the immune tolerance gourp after transplantation, but showed no statistical difference. 5) OS of donors for KIR- Bx genotype was higher than the donor for KIR- AA genotype, both compared statistically significant(p = 0.034).【Conclusions】Except for KIR-BB don’t express KIR3DL1, KIR3DL1 genes existed in KIR- AA and KIR-AB.In KIR3DL1 ligands HLA-BW4/BW6 mixed to form the highest proportion,present the skewness distribution.KIR3DL1 expression level in patients with hematologic malignancies at first visit was significantly lower than donor, OS of Bx genotypes was higher than the donor for KIR- AA genotype after transplantation. KIR3DL1 expression level in relapse group was lower than that of the immune tolerance group.Analysis of KIR3DL1 expression level from the angle of the KIR gene-type,haplo-type and KIR/HLA model had certain clinical value to predict prognosis of unrelated donor allogeneic hematopoietic stem cell transplantation.