China Oncology ›› 2020, Vol. 30 ›› Issue (8): 577-585.doi: 10.19401/j.cnki.1007-3639.2020.08.003

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Relationship between epigenetic modification of SOCS1 and acute myeloid leukemia

ZHANG Xiaohui 1 , LUO Jianmin 2 , SUO Xiaohui 1 , SUN Guofeng 1 , LIU Hongfeng 1 , LI Jing 3 , NIU Guangxu 4   

  1. 1.Department of Hematology, Handan Central Hospital, Handan 056001, Hebei Province, China; 2. Department of Hematology, The Second Hospital of Hebei Medical University, Key Laboratory of Hematology, Shijiazhuang 050000, Hebei Province, China; 3. Department of Oncology, Handan Central Hospital, Handan 056001, Hebei Province, China; 4. Department of Pathology, Handan Central Hospital, Handan 056001, Hebei Province, China
  • Online:2020-08-30 Published:2020-09-03
  • Contact: ZHANG Xiaohui E-mail: zhangxiaohuiqq@163.com

Abstract: Background and purpose: Suppressor of cytokine signaling 1 (SOCS1) is a widely recognized tumor suppressor gene. This study aimed to explore the relationship between the epigenetic modification of SOCS1 gene and acute myeloid leukemia (AML). Methods: We utilized several techniques such as reverse transcription polymerase chain reaction (RT-PCR), methylation-specific PCR (MS-PCR), Western blot, cell culture, drug treatment, cell viability assay and gene knock-out to analyze the expression of SOCS1. We analyzed 110 AML patients treated in the Department of Hematology, Handan Central Hospital, and Department of Hematology, The Second Hospital of Hebei Medical University, from Feb. 2016 to Dec. 2018, and leukemia cell lines U937 and THP-1 to study the underlying molecular mechanism of SOCS1 in AML. We also utilized the changes of DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3a (DNMT3a) and histone deacetylase 1 (HDAC1). Results: We found that SOCS1 gene methylation rate in initial treatment group (IT) and relapsed/refractory group (RR) group was significantly higher than that in remission group (RE) and normal control group (NC) (48% and 80% vs 0% and 0% respectively). Moreover, the mRNA and protein expression were significantly lower in IT and RR when compare to RE and NC. We also found that the expressions of DNMT1, DNMT3a and HDAC1 were negatively affected by SOCS1. SOCS1 methylation was negatively correlated with complete remission (CR) after treatment. After drug treatment, the growth of tumor cells was inhibited with the decrease of DNMT1, DNMT3a and HDAC1 expressions and the recovery of SOCS1 gene expression. Conclusion: SOCS1 gene methylation and deacetylation caused gene silencing of SOCS1 which promoted the growth and proliferation of acute myeloid leukemia cells.

Key words: Acute myeloid leukemia, Suppressor of cytokine signaling 1, Methylation, DNA methyltransferase 1, DNA methyltransferase 3a, Histone deacetylase 1