Contributions
Abstract: PB1937
Type: Publication Only
Background
Human Leukocyte Antigens - HLA molecules present pathogens and tumor-derived peptides to T-cells, which initiates an adaptive immune response. Besides the immune response, many studies have shown a correlation between HLA and different etiologies of many diseases, including autoimmune, infectious, neoplastic, and idiopathic diseases. Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder characterized by t (9; 22) translocation. This translocation results in the formation of the chimeric bcr/abl gene encoding the p210 fusion protein. p210 is thought to be a potential endogenous immunogenic tumor-specific antigen. Because these fusion proteins contain peptide sequences that are foreign to the immune system, they may produce a tumor-specific cytotoxic T cell response when presented by the patient's HLA molecules. Some in vitro studies indicate that HLA molecules may play a key role in the immune response to CML cells. Many clinical studies have reported a relationship between CML and specific HLA alleles that differ from race to race. In these studies, some HLA alleles are suggested to decrease the occurrence of CML and some HLA alleles are found to be associated with the onset of the disease. However, despite intensive research and several Meta-analyses, the role of HLA in the pathogenesis of CML is still unclear.
Aims
In this study, we aimed to investigate the frequency of class I and class II HLA alleles and to evaluate their effect on survival in the CML patients.Methods
One hundred and seventy patients with CML diagnosis were included in our study. The age range of the patient group was 19-79 and the median age was 45 years and 50% of the patients were female. The control group (n = 426) consisted of healthy donors and 49.5% were female. A comparison of the class I and class II HLA allele types between the patient and control groups was done. Patients and donors in the control group underwent HLA typing by PCR-SSP before the year 2010 and by PCR-SSO after the year 2010.
Results
HLA- B*52, B*55, DRB1*03, DRB1 ⃰16 alleles had higher frequencies in the CML patients when compared with the control group and, HLA-A*68, B ⃰35, C ⃰04, C*16, DRB1*04, DRB1*11 ve DQB1*03 allele frequencies were decreased. After the Bonferroni correction, the decrease in the frequency of DQB1*03 allele was found to be statistically significant. (p <0.008; after Bonferroni correction) Overall survival rates for a median follow-up of ten years in patients with and without HLA-DQB1-03 alleles, were 87.5% and 88.5%, respectively, and there was no statistically significant difference between the two groups in terms of overall survival (P = 0.57)
Conclusion
The decrease in the frequency of DQB1*03 alleles in CML patients evaluated in our study suggests that the expression of this allele may have a protective effect for the development of CML. Possibly, the immune response occurring in the presence of the presentation of bcr/abl-derived peptides via DQB1-03 is protective against the development of CML. However, DQB1-03 expression had no effect on the duration of survival in patients receiving tyrosine kinase inhibitors. In light of these results, larger studies addressing the effects of HLA allele expression on the disease course and response to treatment in CML patients are necessary for our population.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, HLA, MHC
Abstract: PB1937
Type: Publication Only
Background
Human Leukocyte Antigens - HLA molecules present pathogens and tumor-derived peptides to T-cells, which initiates an adaptive immune response. Besides the immune response, many studies have shown a correlation between HLA and different etiologies of many diseases, including autoimmune, infectious, neoplastic, and idiopathic diseases. Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder characterized by t (9; 22) translocation. This translocation results in the formation of the chimeric bcr/abl gene encoding the p210 fusion protein. p210 is thought to be a potential endogenous immunogenic tumor-specific antigen. Because these fusion proteins contain peptide sequences that are foreign to the immune system, they may produce a tumor-specific cytotoxic T cell response when presented by the patient's HLA molecules. Some in vitro studies indicate that HLA molecules may play a key role in the immune response to CML cells. Many clinical studies have reported a relationship between CML and specific HLA alleles that differ from race to race. In these studies, some HLA alleles are suggested to decrease the occurrence of CML and some HLA alleles are found to be associated with the onset of the disease. However, despite intensive research and several Meta-analyses, the role of HLA in the pathogenesis of CML is still unclear.
Aims
In this study, we aimed to investigate the frequency of class I and class II HLA alleles and to evaluate their effect on survival in the CML patients.Methods
One hundred and seventy patients with CML diagnosis were included in our study. The age range of the patient group was 19-79 and the median age was 45 years and 50% of the patients were female. The control group (n = 426) consisted of healthy donors and 49.5% were female. A comparison of the class I and class II HLA allele types between the patient and control groups was done. Patients and donors in the control group underwent HLA typing by PCR-SSP before the year 2010 and by PCR-SSO after the year 2010.
Results
HLA- B*52, B*55, DRB1*03, DRB1 ⃰16 alleles had higher frequencies in the CML patients when compared with the control group and, HLA-A*68, B ⃰35, C ⃰04, C*16, DRB1*04, DRB1*11 ve DQB1*03 allele frequencies were decreased. After the Bonferroni correction, the decrease in the frequency of DQB1*03 allele was found to be statistically significant. (p <0.008; after Bonferroni correction) Overall survival rates for a median follow-up of ten years in patients with and without HLA-DQB1-03 alleles, were 87.5% and 88.5%, respectively, and there was no statistically significant difference between the two groups in terms of overall survival (P = 0.57)
Conclusion
The decrease in the frequency of DQB1*03 alleles in CML patients evaluated in our study suggests that the expression of this allele may have a protective effect for the development of CML. Possibly, the immune response occurring in the presence of the presentation of bcr/abl-derived peptides via DQB1-03 is protective against the development of CML. However, DQB1-03 expression had no effect on the duration of survival in patients receiving tyrosine kinase inhibitors. In light of these results, larger studies addressing the effects of HLA allele expression on the disease course and response to treatment in CML patients are necessary for our population.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, HLA, MHC