Abstract
ObjectiveTo reveal the contributing role of METTL3 gene SNPs in pediatric ALL risk.Patients and MethodsA total of 808 pediatric ALL cases and 1,340 cancer-free controls from five hospitals in South China were recruited. A case-control study by genotyping three SNPs in the METTL3 gene was conducted. Genomic DNA was abstracted from peripheral blood. Three SNPs (rs1263801 C>G, rs1139130 A>G, and rs1061027 A>C) in the METTL3 gene were chosen to be detected by taqman real-time polymerase chain reaction assay.ResultsThat rs1263801 C>G, rs1139130 A>G, and rs1061027 A>C polymorphisms were significantly associated with increased pediatric ALL risk was identified. In stratification analyses, it was discovered that rs1263801 CC, rs1061027 AA, and rs1139130 GG carriers were more likely to develop ALL in subgroups of common B-ALL, MLL gene fusion. Rs1263801 CC and rs10610257 AA carriers were more possible to increase the risk of ALL in subgroups of low hyperdiploid, and all of these three SNPs exhibited a trend toward the risk of ALL. All of these three polymorphisms were associated with the primitive/naïve lymphocytes and MRD in marrow after chemotherapy in ALL children. Rs1263801 CC and rs1139130 AA alleles provided a protective effect on MRD ≥0.01% among CCCG-treated children. As for rs1139130, AA alleles provided a protective effect on MRD in marrow ≥0.01% on 33 days and 12 weeks among CCCG-treated children, but provided a risk effect on MRD in the marrow ≥0.01% among SCCLG-treated children. As for rs1263801 CC and rs1139130 AA, these two alleles provided a protective effect on MRD in the marrow ≥0.01% among CCCG-treated children.ConclusionIn this study, we revealed that METTL3 gene polymorphisms were associated with increased pediatric ALL risk and indicated that METTL3 gene polymorphisms might be a potential biomarker for choosing ALL chemotherapeutics.
Highlights
Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer in the world; in China, it accounts for 70–80% of pediatric leukemia [1]
As for rs1139130, AA alleles provided a protective effect on MRD in marrow ≥0.01% on 33 days and 12 weeks among Children Cancer Group chemotherapeutics (CCCG)-treated children but provided a risk effect on MRD in marrow ≥0.01% among South China Children Leukemia Group chemotherapeutics (SCCLG)-treated children
These results indicated that SCCLG chemotherapeutics is more suitable for rs1263801 CC and rs1139130 AA carriers; CCCG chemotherapeutics is more efficient for rs1061027 AA carriers
Summary
Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer in the world; in China, it accounts for 70–80% of pediatric leukemia [1]. ALL can be classified by immune cell phenotype as B-cell ALL and T-cell ALL. B-cell ALL is the most common ALL; T-cell ALL is typically more aggressive [2]. As traditional chemotherapy combined with novel therapies makes great progress, higher survival rates and reduced morbidities have been achieved in ALL. The 5-year overall survival rate of ALL children younger than 14 years has been achieved >90% [3]. Recurrence occurs in 15–20% of ALL children, and 15% pediatric ALL patients were therapeutic failures, which resulted in early age mortality [4]. ALL is characterized by multiple genetic alterations [5]
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