Genetic Polymorphisms in Wnt Signaling Pathway and Acute Leukemia

Objective To determine the impacts of Wnt signaling pathway products-polymorphisms of rs4135385, rs11079571 and rs7832767 located in β-catenin gene (CTNNB1), Axin gene (AXIN2), and secreted frizzled-related protein gene (SFRP1) on the risk and treatment outcomes of acute leukemia. Methods Bone marrows (volume 1-1.5 mL) were collected from 372 untreated patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), and peripheral blood samples (2.0 mL) were obtained from 401 healthy controls for the purpose of total DNA extraction. Polymorphisms of rs4135385, rs11079571 and rs7832767 located in CTNNB1, AXIN2 and SFRP1 were genotyped with high-resolution melting method (HRM). Chi-square analyses were performed to compare the genotype and allele distributions of the three single nucleotides (SNPs) between the leukemia patients and healthy controls. Single factor variance tests were performed to compare the differences in clinical features among different genotype groups. Complete remission (CR) rates after induction chemotherapy were also compared between different genotype groups using Chi-square tests. Results No significant differences were found between the leukemia patients and healthy controls in the frequencies of alleles and genotypes of CTNNB1 rs4135385, SFRP1 rs7832767 polymorphisms. Those with A allele in AXIN2 rs11079571 polymorphism was less likely to have acute myelomonocytic/monocytic leukemia than those with G allele (P=0.016, OR=0.677, 95%CI：0.439-0.930). Acute bead monocyte/mononuclear cell leukemia （AML-M4/5）patients with AA genotype presented higher platelet count (P=0.040), and higher complete remission rate after chemotherapy (P=0.040), compared with the patients with AG and GG genotypes. Conclusion AML-M4/5 patients have less frequency of A allele in AXIN2 rs11079571 polymorphism than healthy controls. Patients carrying A allele have higher platelet counts and higher sensitivity to chemotherapy.