IKZF1 Gene in Childhood B-cell Precursor Acute Lymphoblastic Leukemia: Interplay between Genetic Susceptibility and Somatic Abnormalities

Abstract

SNPs in are associated with inherited susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Besides, somatic copy number abnormalities (CNA) in genes related to lymphopoiesis (e.g.,) impact patient's outcome. Therefore, this study aimed to investigate an association between germline susceptibility and CNAs in BCP-ALL. The SNPs (rs11978267 and rs4132601) were genotyped in 276 cases and 467 controls. Bone marrow samples were used to determine the presence of somatic abnormalities. The transcript levels were quantified and associated with the SNPs and CNAs. Categorical variables were compared by χ test. ORs were estimated with unconditional logistic regression with 95% confidence interval (CI). The variant allele of rs4132601 conferred increased risk of BCP-ALL (OR, 2.09; 95% CI, 1.16-3.74). Individuals with either rs11978267 or rs4132601 had an increased risk for harboring deletion (OR, 2.80; 95% CI, 1.25-6.23 and OR, 2.88; 95% CI, 1.24-6.69, respectively). Increased risks were observed for individuals harboring both and deletions (OR, 4.90; 95% CI, 1.65-14.55, rs11978267 and OR, 5.80; 95% CI, 1.94-17.41, rs4132601). Germline genetic variation increases the risk for childhood ALL in general, but also acts as a susceptibility factor bound for risk of specific somatic alterations. These findings provide new insight into the development of childhood ALL regarding causal variants and the biological basis of the risk association, offering the opportunity for future tailored research. .

Rs4846049 Polymorphism at the 3′-UTR of MTHFR Gene: Association with Susceptibility to Childhood Acute Lymphoblastic Leukemia

“…Moreover, a recent study indicated there was an association between IKZF1 rs4132601 polymorphism and age at diagnosis of childhood ALL, with the patients older in carriers of GT and TT genotypes in comparison with carriers of GG genotype [33]. Also, the GT and TT genotypes were found to be risky for the development of ALL in patients aged >9 years [34]. Thus, we also divided the patients into two groups according to the age range.…”

IKZF1 Rs4132601 Polymorphism and Susceptibility to Acute Lymphocytic Leukemia in Children: A Meta-analysis

“…According to the criteria, 9 articles were selected, 11,[19][20][21][22][23][24][25][26] including 5 articles in Caucasian children, 3 articles in Asian children, and 1 article in African children. A total of 2281 children with ALL and 2923 controls were selected.…”

Expression of chimeric genes in bone marrow cells of children with acute lymphoblastic leukemia upon cytostatic therapy

“…Acute lymphoblastic leukemia (ALL) is the most common malignant pediatric neoplasm; the ALL development is connected with various somatic gene defects [1], which lead to the increased proliferation and disruption of the differentiation program of lymphopoiesis progenitors [2].…”