| Abstract |
Acute Lymphoblastic Leukemia is the most common pediatric malignancy and is characterized by the
proliferation of immature lymphocytes (lymphoblasts), which replace the normal elements of the bone
marrow. There have been great leaps in the management and prognosis of childhood ALL over the last
50 years, which has resulted in improved treatment rates from 10% to 90%, but still remains a major
cause of morbidity and mortality, because of disease relapse. Much progress has been made the last
decade in understanding the biology of ALL and the genetic basis of leukemogenesis and response to
treatment. The disease is characterized by clinical and biological heterogeneity, which is due to various
genetic changes.
Apoptosis is defined as programmed cell death without inflammatory response. There are two
pathways of apoptosis, internal (mitochondrial) and external (cytoplasmic), which act collaboratively to
remove ineffective cells from the organism. In lymphoma, leukemia and solid tumors, either the
internal or external pathway of apoptosis may be involved, as well as the deregulation of expression or
function of caspase antagonist’s pathways. Alterations in the mechanisms of programmed cell death
play an important role in pathogenesis and progression of hematological neoplasms. Caspases are a
family of cysteine proteases whose functions are strongly associated with programmed cell death.
Polymorphisms in apoptosis genes may contribute to the risk of disease and, more specifically, the
strong link between genetic diversity and susceptibility to ALL has been identified. Polymorphisms in
caspase genes may be involved in various types of cancer, and while some caspase mutations that
reduce apoptotic activity may play a protective role in the tumor, they may have a stronger anticancer
response by reducing apoptosis of tumor lymphocytes. Caspase 8 plays an important role in apoptosis
and several studies have been performed to identify the relationship between polymorphisms in the caspase 8 gene (CASP8) and different types of cancer. Caspase 10 is the only caspase that shares
homologous death – effector domains with caspase 8 and somatic mutations in caspase 10 have been
observed in many cancers.
The purpose of the present research 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.
The patient group consisted of 50 children and adolescents with ALL and 100 individuals composed the
control group. Genomic DNA was isolated from the samples of both groups and both genetic locis were
amplified by the Polymerase Chain Reaction method. The PCR products were then incubated with the
appropriate restriction enzyme.
Statistical analysis showed a correlation between G allele of caspase 8 rs1045485 SNP and ALL (p =
0.0002). Caspase 10 rs13006529 polymorphism was also found to be associated with the disease, more
specifically the AT genotype (p = 0.011) and the TT genotype (p=0.048), but also with allele T (p <
0.0001). Therefore, the present study showed that caspase 8 rs1045485 polymorphism and caspase 10
rs13006529 polymorphism are related to the disease at the level of genotypes or alleles. Further study
of these polymorphisms in children and adolescents with ALL would be of great interest, in order to see
if their existence is related to the development of the disease in Greek population.
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Μελέτη των πολυμορφισμών της κασπάσης 8 (CASP8) και 10 (CASP10) στην οξεία λεμφοβλαστική λευχαιμία παιδιών και εφήβων
