Contributions
Abstract: PB1903
Type: Publication Only
Background
It is a well-known fact that natural killer (NK) cells have anti-tumour activities. This activity of NK cells is regulated by specific receptors called KIR (Killer Immunoglobulin-like receptors). The proportion between the activatory and inhibitory receptors, binding strength of receptors to the given ligands and the balance between the composite signals determine the health and ailment attitudes of NK cells. Previous studies have shown decreased expression of HLA class 1 molecules on leukemic cells. It has been postulated that lack of clearance of the leukemia cells could be caused by the lack of activity of the NK cells, which may be the result of the genetically determined KIR/HLA ligand content.
Aims
In this study we investigated the association of KIR genes with acute (AML) and chronic myeloid leukemia (CML) patients in Turkish population and also tried to correlate with the clinical outcomes.
Methods
Patient group consisted of patients with AML (n=34) (M/F: 31/15); mean age 56 years, and CML (n=46) (M/F: 18/16; mean, 52 years. Age and sex matched 100 healthy controls were also included. DNA from venous blood samples was extracted by DNA isolation kit (QIAGEN Vertriebs GmbH, Vienna, Austria). Genotyping of KIR genes was performed using the multiplex KIRSSO typing kit from Tepnel Lifecodes Corporation (CT, USA). The statistical significances were assessed through Pearson’s homogeneity chi-squared test.
Results
The presence of KIR2DL3 was significantly increased in the leukemia patients relative to the controls (91.3% vs 78%, OR = 0.340, P =0.016). In CML patients, KIR2DL3 gene frequency was significantly higher compared to controls (93.5% vs 78.0%, OR=0.247, P =0.031). In addition, presence of KIR2DL2 and KIR2DS2 was significantly decreased in the CML patients compared with controls with the same level of significance (34.8% vs 52.0%, OR = 2.031, P = 0.053). In CML patients who achieved MMR ( BCR-ABL1≤0.1% at 12 months of treatment ), gene frequency of KIR2DL2 and KIR2DS2 was lower compared to the control group (33.3% vs 52.0%, P =0.054, for both analysis ); whereas in those without MMR gene frequency was 40%, P >0.05). CML patients without MMR had a higher frequency for KIR2DS1 compared to controls (70.0% vs 35.0%, P =0.041) which was 36.11% for those patients with MMR. There were no associations of KIR AA and Bx genotypes between leukemia patients and controls. The genotypic associations for AML patients were not significant.
Conclusion
KIR2DL2 and KIR2DS2 were suggested in previous studies as being markers for the much more activating haplotype for NK cells. Decreased gene frequencies of KIR2DL2 and KIR2DS2 in CML patients in our study support these findings as such that their reduction would presumably lead to more inhibition with tyrosine kinase inhibitors. Better treatment outcomes observed in this study as reflected by a higher frequency of MMR in patients who had lower KIR2DL2 and KIR2DS2 frequencies suggest that prognostic information could be available by further understanding the role KIR interactions in leukemic patients. In addition our results suggest that increased frequency of a weak inhibitory receptor KIR2DL3 in leukemic patients might contribute decreased NK cell activity against leukemia cells.
Session topic: 7. Chronic myeloid leukemia – Biology & Translational Research
Keyword(s): Killer immunoglobulin receptors (KIR), Leukemia, Myeloid
Abstract: PB1903
Type: Publication Only
Background
It is a well-known fact that natural killer (NK) cells have anti-tumour activities. This activity of NK cells is regulated by specific receptors called KIR (Killer Immunoglobulin-like receptors). The proportion between the activatory and inhibitory receptors, binding strength of receptors to the given ligands and the balance between the composite signals determine the health and ailment attitudes of NK cells. Previous studies have shown decreased expression of HLA class 1 molecules on leukemic cells. It has been postulated that lack of clearance of the leukemia cells could be caused by the lack of activity of the NK cells, which may be the result of the genetically determined KIR/HLA ligand content.
Aims
In this study we investigated the association of KIR genes with acute (AML) and chronic myeloid leukemia (CML) patients in Turkish population and also tried to correlate with the clinical outcomes.
Methods
Patient group consisted of patients with AML (n=34) (M/F: 31/15); mean age 56 years, and CML (n=46) (M/F: 18/16; mean, 52 years. Age and sex matched 100 healthy controls were also included. DNA from venous blood samples was extracted by DNA isolation kit (QIAGEN Vertriebs GmbH, Vienna, Austria). Genotyping of KIR genes was performed using the multiplex KIRSSO typing kit from Tepnel Lifecodes Corporation (CT, USA). The statistical significances were assessed through Pearson’s homogeneity chi-squared test.
Results
The presence of KIR2DL3 was significantly increased in the leukemia patients relative to the controls (91.3% vs 78%, OR = 0.340, P =0.016). In CML patients, KIR2DL3 gene frequency was significantly higher compared to controls (93.5% vs 78.0%, OR=0.247, P =0.031). In addition, presence of KIR2DL2 and KIR2DS2 was significantly decreased in the CML patients compared with controls with the same level of significance (34.8% vs 52.0%, OR = 2.031, P = 0.053). In CML patients who achieved MMR ( BCR-ABL1≤0.1% at 12 months of treatment ), gene frequency of KIR2DL2 and KIR2DS2 was lower compared to the control group (33.3% vs 52.0%, P =0.054, for both analysis ); whereas in those without MMR gene frequency was 40%, P >0.05). CML patients without MMR had a higher frequency for KIR2DS1 compared to controls (70.0% vs 35.0%, P =0.041) which was 36.11% for those patients with MMR. There were no associations of KIR AA and Bx genotypes between leukemia patients and controls. The genotypic associations for AML patients were not significant.
Conclusion
KIR2DL2 and KIR2DS2 were suggested in previous studies as being markers for the much more activating haplotype for NK cells. Decreased gene frequencies of KIR2DL2 and KIR2DS2 in CML patients in our study support these findings as such that their reduction would presumably lead to more inhibition with tyrosine kinase inhibitors. Better treatment outcomes observed in this study as reflected by a higher frequency of MMR in patients who had lower KIR2DL2 and KIR2DS2 frequencies suggest that prognostic information could be available by further understanding the role KIR interactions in leukemic patients. In addition our results suggest that increased frequency of a weak inhibitory receptor KIR2DL3 in leukemic patients might contribute decreased NK cell activity against leukemia cells.
Session topic: 7. Chronic myeloid leukemia – Biology & Translational Research
Keyword(s): Killer immunoglobulin receptors (KIR), Leukemia, Myeloid