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<p>The immune system is essential for immuno-surveillance and the generation of anti-tumor immunity. However, the role of immune-related single-nucleotide polymorphisms (SNPs) in the susceptibility and progression of acute lymphoblastic leukemia (ALL) is currently unknown. Here, we selected and analyzed 28 immune-related SNPs in 201 ALL patients and 228 healthy controls. We uncovered five important SNPs related to ALL susceptibility, including in TGFB1(rs1800469), GATA3 (rs3824662), TNFA (rs1800629), PARP1 (rs1805414), and IL6R (rs2228145). PARP1 (rs1805414) and GATA3 (rs3824662) were also associated with the ALL immunophenotype. Additionally, STAT3 (rs744166) and TMPRSS2 (rs12329760) significantly contributed to the susceptibility of Philadelphia chromosome-positive (Ph+) ALL. More importantly, MAVS (rs7269320) and NF-KBIA (rs2233406) were remarkably associated with the overall survival (OS) of ALL patients. Furthermore, ITGAM (rs4597342), PTPN22 (rs2488457), STAT5B (rs6503691), and MAVS (rs7269320) were significantly associated with the progression-free survival (PFS) of ALL patients. In the training cohort, we built a prognostic classifier, which identified five features. The five selected SNPs were related to GATA3, IL-6R, ITGAM, PTPN22, and STAT1. Moreover, the five SNP-based classifiers demonstrated a higher accuracy in predicting the OS and the PFS. In addition, we found that the mRNA expression of GATA3 gene was significantly higher in ALL patients than in healthy controls. GATA3 mRNA expression were also elevated in ALL patients with CA and AA genotypes. Our findings suggest that immune-related genetic polymorphisms contribute to the prognosis and treatment of ALL and could also serve as a valuable disease predictor.</p>

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Immune-related genetic single-nucleotide polymorphisms contribute to prognosis and response to chemotherapy in patients with acute lymphoblastic leukemia

  • 期刊论文

  • 发表日期：

    2025年4月29日

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  • Amin Zhang,
  • Wancheng Liu,
  • Can Can,
  • Xiaodong Guo,
  • Hexiao Jia,
  • Yihong Wei,
  • Hanyang Wu,
  • Xinyu Yang,
  • Chunyan Ji,
  • Daoxin Ma

摘要

The immune system is essential for immuno-surveillance and the generation of anti-tumor immunity. However, the role of immune-related single-nucleotide polymorphisms (SNPs) in the susceptibility and progression of acute lymphoblastic leukemia (ALL) is currently unknown. Here, we selected and analyzed 28 immune-related SNPs in 201 ALL patients and 228 healthy controls. We uncovered five important SNPs related to ALL susceptibility, including in TGFB1(rs1800469), GATA3 (rs3824662), TNFA (rs1800629), PARP1 (rs1805414), and IL6R (rs2228145). PARP1 (rs1805414) and GATA3 (rs3824662) were also associated with the ALL immunophenotype. Additionally, STAT3 (rs744166) and TMPRSS2 (rs12329760) significantly contributed to the susceptibility of Philadelphia chromosome-positive (Ph+) ALL. More importantly, MAVS (rs7269320) and NF-KBIA (rs2233406) were remarkably associated with the overall survival (OS) of ALL patients. Furthermore, ITGAM (rs4597342), PTPN22 (rs2488457), STAT5B (rs6503691), and MAVS (rs7269320) were significantly associated with the progression-free survival (PFS) of ALL patients. In the training cohort, we built a prognostic classifier, which identified five features. The five selected SNPs were related to GATA3, IL-6R, ITGAM, PTPN22, and STAT1. Moreover, the five SNP-based classifiers demonstrated a higher accuracy in predicting the OS and the PFS. In addition, we found that the mRNA expression of GATA3 gene was significantly higher in ALL patients than in healthy controls. GATA3 mRNA expression were also elevated in ALL patients with CA and AA genotypes. Our findings suggest that immune-related genetic polymorphisms contribute to the prognosis and treatment of ALL and could also serve as a valuable disease predictor.