|
|
Study of HLA antigens and KIR genes in a donors and recipients of bone marrow
Kroulíková, Zuzana ; Vraná, Milena (advisor) ; Froňková, Eva (referee)
HLA and KIR genes are highly polymorphic regions within the human genome. Protein products of these genes play a critical role in hematopoietic stem cell transplantation. Genetic HLA match is a major barrier to engraftment and influences the outcome of this therapy. Therefore it is necessary to genotype donors and recipients selected for hematopoietic stem cell transplantation. Today HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes are tested by modifications of polymerase chain reaction or by sequence-based typing methods on the level of high- or low-resolution. Donors registered in bone marrow registries are selected on the basis of a 10/10 match. Donors KIR genotype leads to a better outcome, to relapse-free survival and overall survival in treatment of patients with acute myeloid leukemia. A better protection against relapse is achieved by Cen-B/B donor haplotype. Therefore KIR typing by polymerase chain reaction is used and the genotype is compared with the IMGT/KIR database by an online B- content calculator. Donors are divided in groups according to their genotype and their influence on the success of treatment for acute myeloid leukemia. The study of polymorphic systems and the development of genotyping donors and recipients significantly improve the outcome of hematopoietic stem cell...
|
|
|
Study of HLA antigens and KIR genes in a donors and recipients of bone marrow
Kroulíková, Zuzana ; Vraná, Milena (advisor) ; Froňková, Eva (referee)
HLA and KIR genes are highly polymorphic regions within the human genome. Protein products of these genes play a critical role in hematopoietic stem cell transplantation. Genetic HLA match is a major barrier to engraftment and influences the outcome of this therapy. Therefore it is necessary to genotype donors and recipients selected for hematopoietic stem cell transplantation. Today HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes are tested by modifications of polymerase chain reaction or by sequence-based typing methods on the level of high- or low-resolution. Donors registered in bone marrow registries are selected on the basis of a 10/10 match. Donors KIR genotype leads to a better outcome, to relapse-free survival and overall survival in treatment of patients with acute myeloid leukemia. A better protection against relapse is achieved by Cen-B/B donor haplotype. Therefore KIR typing by polymerase chain reaction is used and the genotype is compared with the IMGT/KIR database by an online B- content calculator. Donors are divided in groups according to their genotype and their influence on the success of treatment for acute myeloid leukemia. The study of polymorphic systems and the development of genotyping donors and recipients significantly improve the outcome of hematopoietic stem cell...
|
|
|
Is it possible in clinical practice to perform selection of unrelated donors based on KIR genotypes for AML patients?
FRYČOVÁ, Michaela
Acute myeloid leukemia (AML) is an aggressive malignant disease, during which is for most of the patients only possible treatment the curative allogeneic stem cell transplantation. Besides reaction of the graft against the host is a fundamental limiting factor of the successful transplantation the relapse of the disease. According to several recent published studies, the results of transplantation in patients with AML may be influenced except the HLA genes by others so-called non - HLA genes. Especially there is mounting evidence influence of the donors KIR genes (Killer -cell Immunoglobulin - like receptors) in protection against the relapse after transplantation. HLA and KIR genes are coded on different chromosomes (HLA- sixth chromosome and KIR chromosome 19), therefore are segregated independently and HLA identical donors with recipients usually have different compositions of the KIR genes. Cooley et al. (2010) demonstrated that the specific motifs composition of centromeric and telomeric B haplotypes of KIR genes helps to protect against relapse and increases the chances of complete cure AML. In cases where there are multiple HLA identical unrelated donors (UD) then logically the composition KIR genes by the individual donor could be a criterion in selecting the most appropriate donor, therefore, the one with the greatest potential to protect over the relapse . Based on this study and other data the genetic screening of KIR was started with potential donors, if it was possible to choose from several 10/10 or 10/09 HLA identical UD for the patient. Genotyping was performed by PCR-SSP methodology using commercially available kits. It was performed gene classification 160 preferably identical HLA donors for 55 selected patients with AML. The presence of KIR haplotypes A and B as well as their combinations was determined from the type and number of the KIR genes. All genotypes were entered into the calculator, which allows you to enter up to five potential donors and obtain their assigned into one of three categories according to content KIR B. Groups , "neutral" , "better" , "best" , refer to the appropriate protection against relapse. KIR gene classification in the search for donors revealed 43 donors with AA haplotypes, 90 donors with AB haplotypes and 27 donors with BB haplotypes . After assigning state of the presence KIR B was discovered 107 " neutral " donors , 35 "better " donors and the 18 "best " donors . At 40 (~ 73 %) patients were available donors with the different states of the presence of KIR B. These patients represent a group of patients where the selection criterion of the presence B KIR gene at the donor could be used. We confirmed that the additional selection of HLA-matched unrelated donor on the basis of the content B of KIR genes is feasible. Selection such donor for transplantation may improve the outcome of patients with AML.
|
guest ::
