Understanding the role of genetics in childhood acute lymphoblastic leukemia (Review)

Kampouraki, Eleni; Goulielmos, George N.; Stiakaki, Eftichia

doi:10.3892/wasj.2020.54

Cited by 3 publications

(3 citation statements)

References 65 publications

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“…4 , 14–25 GSTM1 polymorphism has shown increased risk of developing ALL in children while GSTT1 was found not to predispose to childhood ALL. 26 Additionally, patients with combined genotype ( GSTT1 null and GSTM1 null) were found to be at slight increased risk of relapse. 27 In a meta-analysis of 30 published case control studies, significantly increased risk of ALL showed association with GSTM1 and GSTT1 null genotypes {pooled ORs 1.24 (95% CI 1.17–1.31) and 1.30 (95% CI 1.06–1.60), respectively}.…”

Section: Introductionmentioning

confidence: 99%

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism

Abdalhabib

Alzahrani

Alanazi

et al. 2022

PGPM

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Purpose Glutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1 , and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL. Patients and Methods This case–control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control. Results The genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = <0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42–29.74, P < 0.001). Conclusion Irrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.

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Section: Introductionmentioning

confidence: 99%

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism

Abdalhabib

Alzahrani

Alanazi

et al. 2022

PGPM

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“…Recent gene association studies that examined cancer risk have focused on the effects of single-nucleotide polymorphisms (SNPs) of genes involved in the regulation of inflammation and tumor suppression, such as chemokines, TP53 and cytochrome P450s (CYPs) (8,9). Chemokines induce the migration of endothelial and tumor cells and consequently influence distal metastasis (10).…”

Section: Introductionmentioning

confidence: 99%

Role of CXCL12, TP53 and CYP1A1 gene polymorphisms in susceptibility to pediatric acute lymphoblastic leukemia

et al. 2021

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Acute lymphoblastic leukemia (ALL) is the most common type of childhood leukemia and represents one third of all pediatric malignancies. Epidemiological studies have shown that various genetic factors play a crucial role in leukemogenesis. Recent genetic association studies on cancer risk have focused on the effects of single-nucleotide polymorphisms (SNPs) in genes that regulate inflammation and tumor suppression, such as chemokines, TP53 and cytochrome P450s (CYPs). Genetic polymorphisms in the 3' untranslated region of the C-X-C motif chemokine ligand 12 (CXCL12; rs1801157) and TP53 (rs1042522) genes have been suggested to influence the risk of ALL in children, while other studies have indicated an association between the CYP1 subfamily A member 1 (CYP1A1) * 2C (rs1048943) allele and leukemia risk. The aim of the present study was to investigate the possible association of rs1801157 (CXCL12), rs1042522 (TP53) and rs1048943 (CYP1A1 * 2C) SNPs with an increased susceptibility of developing ALL. These SNPs were analyzed in 86 children or adolescent patients with ALL and 125 control subjects by PCR-restriction fragment length polymorphism and allelic-specific chain reaction techniques. A higher frequency of CYP1A1 * 2C heterozygotes and TP53 rare homozygotes, which include the proline (Pro)/Pro genotype, was observed among children with ALL and control subjects, whereas no significant differences were observed for the CXCL12 SNP. Furthermore, the analysis of various allelic combinations of the aforementioned gene polymorphisms demonstrated a markedly increased risk of developing ALL in children. In conclusion, the present study demonstrated that there was a strong association between CYP1A1 * 2C heterozygotes, as well as the TP53 Pro/Pro genotype, and an increased susceptibility for pediatric ALL in Caucasians.

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“…Several gene polymorphism have been investigated concerning susceptibility to ALL including SNPs of carcinogen metabolism genes, folate metabolism genes, DNA repair genes, regulators of lymphoid cell differentiation, tumor suppressors ,transcriptional factors and chemokines, in addition ,various SNPs participating in the metabolism of antileukemic agents inducing therapy toxicity , discontinuation of therapy with risk of relapse (Kampouraki et al,2020).…”

Section: Introductionmentioning

confidence: 99%

Cyclin D1 G870A Polymorphism: Relation to the Risk of ALL Development, Prognosis Impact, and Methotrexate Cytotoxicity

Menshawy

Marghany

Sarhan

et al. 2020

Asian Pac J Cancer Prev

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Nowadays, Pharmacogenomics tests, including Genome-wide association studies (GWAS), have a direct identification role in genetic alterations, treatment efficacy, cytotoxicity, prognosis, etc. However, the current knowledge gives little data about how genomic determinants can affect ALL susceptibility, chemotherapy, and chance of relapse (Wu and Li, 2018). Methotrexate (MTX) forms the backbone of maintenance cycles in childhood acute lymphoblastic leukemia (ALL) chemotherapy, including interim maintenance (Mandal et al., 2020). Major adversities include cytopenias, mucositis, liver toxicity, renal toxicity and skin toxicity. These toxicities enquire dose modification or omission (burn out) MTX-related toxicities may be determined by several factors like dose, duration, genetic susceptibility and risk factors (Vaishnavi et al ., 2018).

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Understanding the role of genetics in childhood acute lymphoblastic leukemia (Review)

Cited by 3 publications

References 65 publications

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism

Role of CXCL12, TP53 and CYP1A1 gene polymorphisms in susceptibility to pediatric acute lymphoblastic leukemia

Cyclin D1 G870A Polymorphism: Relation to the Risk of ALL Development, Prognosis Impact, and Methotrexate Cytotoxicity

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