Contributions
Abstract: PB1351
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Biology & Translational Research
Background
In the past 50 years great advances have been achieved in the management and prognosis of Acute Lymphoblastic Leukemia (ALL) in children, resulting in improved treatment outcome of up to 90%. However ALL still remains a major cause of morbidity and mortality in children, specially in disease relapse.Major progress has been made in the last decade in understanding the biology of ALL, the genetic basis of leukemogenesis and the response to treatment. Epidemiological studies of possible risk factors in acute leukemia, proved that genetic factors play a crucial role in leukemogenesis. Alterations in the regulation of apoptosis and the deregulation of expression or function of caspase antagonists’ pathways seem to play an important role in the pathogenesis and progression of hematological malignancies. Caspases are a family of cysteine proteases whose functions are strongly associated with programmed cell death. Polymorphisms in the apoptotic genes may enhance the risk of disease, as implicated by the strong link between genetic diversity and susceptibility to ALL. Caspase 8 plays an important role in apoptosis and several studies have been performed to identify the relationship between polymorphisms in Casp8 gene and different types of cancer. Caspase 10 is the only caspase that shares homologous death–effector domains with caspase 8, while somatic mutations in Casp10 gene have been observed in many cancers.
Aims
The purpose of the present study was to investigate the incidence of rs1045485 polymorphism in exon 10 of the caspase 8 gene and rs13006529 in exon 10 of the caspase 10 gene in children and adolescents with Acute Lymphoblastic Leukemia compared with healthy individuals.
Methods
The patient group consisted of 50 children and adolescents (1.5 to 17.5 years) with ALL and the control group consisted of 100 healthy individuals. Genomic DNA was isolated from periphral blood of participants and the genetic regions harboring the single nucleotide polymorphisms (SNPs) under investigation were amplified with Polymerase Chain Reaction. The PCR product was then digested with the appropriate restriction enzymes (BstUI for rs1045485, SspI for rs13006529). Statistical analysis was performed by using the GraphPad Prism (GraphPad Software, San Diego, CA, USA) program.
Results
Statistic analysis showed an association between the G allele of Casp8 rs1045485 SNP and ALL (p=0.0002, OR=0.381, 95% 0.229-0.633). Statistically significant differences were found between AT and TT genotypes of rs13006529 SNP of Casp10 and ALL (p=0.011, OR=4, CI 95% 1.382-11.380 and p=0.048, OR=0.346, CI 95% 0.127-0.937, respectively), as well as between T allele of the same SNP and ALL (p<0.0001, OR=0.345, CI 95% 0.205-0.578).
Conclusion
The present study showed that both rs1045485 SNP of Casp8 and rs13006529 SNP of Casp10 are associated with the diagnosis of ALL. Further study of these polymorphisms in children and adolescents with ALL would be of great interest, in order to confirm whether they are associated with the disease in the population of Greece.
Keyword(s): Acute lymphoblastic leukemia, Caspase, Childhood, Genetic polymorphism
Abstract: PB1351
Type: Publication Only
Session title: Acute lymphoblastic leukemia - Biology & Translational Research
Background
In the past 50 years great advances have been achieved in the management and prognosis of Acute Lymphoblastic Leukemia (ALL) in children, resulting in improved treatment outcome of up to 90%. However ALL still remains a major cause of morbidity and mortality in children, specially in disease relapse.Major progress has been made in the last decade in understanding the biology of ALL, the genetic basis of leukemogenesis and the response to treatment. Epidemiological studies of possible risk factors in acute leukemia, proved that genetic factors play a crucial role in leukemogenesis. Alterations in the regulation of apoptosis and the deregulation of expression or function of caspase antagonists’ pathways seem to play an important role in the pathogenesis and progression of hematological malignancies. Caspases are a family of cysteine proteases whose functions are strongly associated with programmed cell death. Polymorphisms in the apoptotic genes may enhance the risk of disease, as implicated by the strong link between genetic diversity and susceptibility to ALL. Caspase 8 plays an important role in apoptosis and several studies have been performed to identify the relationship between polymorphisms in Casp8 gene and different types of cancer. Caspase 10 is the only caspase that shares homologous death–effector domains with caspase 8, while somatic mutations in Casp10 gene have been observed in many cancers.
Aims
The purpose of the present study was to investigate the incidence of rs1045485 polymorphism in exon 10 of the caspase 8 gene and rs13006529 in exon 10 of the caspase 10 gene in children and adolescents with Acute Lymphoblastic Leukemia compared with healthy individuals.
Methods
The patient group consisted of 50 children and adolescents (1.5 to 17.5 years) with ALL and the control group consisted of 100 healthy individuals. Genomic DNA was isolated from periphral blood of participants and the genetic regions harboring the single nucleotide polymorphisms (SNPs) under investigation were amplified with Polymerase Chain Reaction. The PCR product was then digested with the appropriate restriction enzymes (BstUI for rs1045485, SspI for rs13006529). Statistical analysis was performed by using the GraphPad Prism (GraphPad Software, San Diego, CA, USA) program.
Results
Statistic analysis showed an association between the G allele of Casp8 rs1045485 SNP and ALL (p=0.0002, OR=0.381, 95% 0.229-0.633). Statistically significant differences were found between AT and TT genotypes of rs13006529 SNP of Casp10 and ALL (p=0.011, OR=4, CI 95% 1.382-11.380 and p=0.048, OR=0.346, CI 95% 0.127-0.937, respectively), as well as between T allele of the same SNP and ALL (p<0.0001, OR=0.345, CI 95% 0.205-0.578).
Conclusion
The present study showed that both rs1045485 SNP of Casp8 and rs13006529 SNP of Casp10 are associated with the diagnosis of ALL. Further study of these polymorphisms in children and adolescents with ALL would be of great interest, in order to confirm whether they are associated with the disease in the population of Greece.
Keyword(s): Acute lymphoblastic leukemia, Caspase, Childhood, Genetic polymorphism