Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To prevent GVHD in BMT from unrelated donors, the matching of HLA between patient and donor is crucial. The appearance of acute GVHD was studied in 51 patients with hematological malignancies who were transplanted with non-T cell purged marrow from HLA-A,B and DR compatible unrelated donors with the assistance of the Tokai Marrow Donor Bank of Nagoya, Japan. Probability of grade II-IV acute GVHD was 32.0% and of grade III-IV acute GVHD was 17.0%. HLA-class II antigen compatibility showed a good correlation with the occurrence of acute GVHD. When the percentage relative response (RR) of MLC between patient and donor (GVHD vector) was < or = 5, grade II-IV acute GVHD was found in only 7.7% of patients (n = 16) and no severe grade III-IV GVHD occurred. Among patients with 6-10% RR (n = 10), 25.9% showed grade II-IV GVHD and 14.3% grade III-IV GVHD. Among patients with > or = 11% RR (n = 20), however, the incidence of grade II-IV acute GVHD reached 51.8% and that of grade III-IV acute GVHD 36.2%. These reactivities of MLC reflected the compatibility of HLA-DRB1 and DPB1. The fact that the incidence of acute GVHD in BMTs from HLA-A,B,DR compatible Japanese pairs was found to be lower than in the USA may be due to less diversity of the genetic background in Japan.
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PMID:Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese. 777 12

The responsible human leukocyte antigen (HLA) locus and the role of killer immunoglobulin-like receptor (KIR) ligand matching on transplantation outcome were simultaneously identified by multivariate analysis in 1790 patients with leukemia who underwent transplantation with T-cell-replete marrow from an unrelated donor (UR-BMT) through the Japan Marrow Donor Program. The graft-versus-leukemia (GVL) effect depended on leukemia cell type. HLA-C mismatch reduced the relapse rate in acute lymphoblastic leukemia (ALL) (hazard ratio [HR] = 0.47; P = .003), and HLA-DPB1 mismatch reduced it in chronic myeloid leukemia (CML) (HR = 0.35; P < .001). In contrast, KIR2DL ligand mismatch in the graft-versus-host (GVH) direction (KIR-L-MM-G) increased in ALL (HR = 2.55; P = .017). An increased rejection rate was observed in KIR2DL ligand mismatch in the host-versus-graft direction (HR = 4.39; P = .012). Acute GVH disease (GVHD) was increased not only in the mismatch of HLA-A, -B, -C, and -DPB1, but also in KIR-L-MM-G. As a whole, the mismatch of HLA-A, -B, and -DQB1 locus and KIR-L-MM-G resulted in increased mortality. In conclusion, not only the mismatch of HLA-C and -DPB1, but also KIR-L-MM-G affected leukemia relapse, which should be considered based on leukemia cell type. Furthermore, KIR-L-MM induced adverse effects on acute GVHD (aGVHD) and rejection, and brought no survival benefits to patients with T-cell-replete UR-BMT.
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PMID:Effects of HLA allele and killer immunoglobulin-like receptor ligand matching on clinical outcome in leukemia patients undergoing transplantation with T-cell-replete marrow from an unrelated donor. 1731 85

Despite HLA allele matching, significant acute GvHD remains a major barrier to successful unrelated donor BMT. We conducted a genome-wide association study (GWAS) to identify recipient and donor genes associated with the risk of acute GvHD. A case-control design (grade III-IV versus no acute GvHD) and pooled GWA approach was used to study European-American recipients with hematological malignancies who received myeloablative conditioning non-T-cell-depleted first transplantation from HLA-A, -B, -C, -DRB1, -DQB1 allele level (10/10) matched unrelated donors. DNA samples were divided into three pools and tested in triplicate using the Affymetrix Genome-wide SNP Array 6.0. We identified three novel susceptibility loci in the HLA-DP region of recipient genomes that were associated with III-IV acute GvHD (rs9277378, P=1.58E-09; rs9277542, P=1.548E-06 and rs9277341, P=7.718E-05). Of these three single nucleotide polymorphisms (SNPs), rs9277378 and rs9277542 are located in non-coding regions of the HLA-DPB1 gene and the two are in strong linkage disequilibrium with two other published SNPs associated with acute GvHD, rs2281389 and rs9277535. Eighteen other recipient SNPs and 3 donor SNPs with a high level of significance (8E-07 or lower) were found. Our report contributes to emerging data showing clinical significance of the HLA-DP region genetic markers beyond structural matching of DPB1 alleles.
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PMID:Novel HLA-DP region susceptibility loci associated with severe acute GvHD. 2759 89