2. Academic Validation
  3. BCL7A inhibits the progression and drug-resistance in acute myeloid leukemia

BCL7A inhibits the progression and drug-resistance in acute myeloid leukemia

  • Drug Resist Updat. 2024 Sep:76:101120. doi: 10.1016/j.drup.2024.101120.
Tushuai Li 1,  Renjie Gao 2,  Kaiwen Xu 3,  Pengpeng Pan 3,  Congcong Chen 3,  Daokuan Wang 4,  Keyi Zhang 3,  Jilei Qiao 4,  Yue Gu 5
Affiliations

Affiliations

  • 1 Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, PR China; School of Biology and Food Engineering, Changshu Institute of Technology, Suzhou 215500, PR China.
  • 2 Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, PR China; Graduate Department, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China.
  • 3 Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, PR China.
  • 4 Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, PR China; The First Clinical School of Anhui Medical University, Hefei 230032, PR China.
  • 5 Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, PR China. Electronic address: yuegu@ahmu.edu.cn.
PMID: 39053383 DOI: 10.1016/j.drup.2024.101120
Abstract

Aims: This study aimed to elucidate the biological roles and regulatory mechanisms of B-cell lymphoma 7 protein family member A (BCL7A) in acute myeloid leukemia (AML), particularly its interaction with polypyrimidine tract binding protein 1 (PTBP1) and the effects on Cancer progression and drug resistance.

Methods: BCL7A expression levels were analyzed in AML tissues and cell lines, focusing on associations with promoter hypermethylation. Interaction with PTBP1 and effects of differential expression of BCL7A were examined in vitro and in vivo. The impacts on cell proliferation, cycle progression, Apoptosis, and differentiation were studied. Additionally, the regulatory roles of BCL7A on interferon regulatory factor 7 (IRF7) and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) were assessed.

Results: BCL7A was downregulated in AML due to promoter hypermethylation and negatively regulated by PTBP1. Upregulation of BCL7A impeded AML cell growth, induced Apoptosis, promoted cell differentiation, and decreased cell infiltration into lymph nodes, enhancing survival in mouse models. Overexpression of BCL7A upregulated IRF7 and downregulated HMGCS1, linking to reduced AML cell malignancy and decreased resistance to cytarabine.

Conclusions: BCL7A acts as a tumor suppressor in AML, inhibiting malignant progression and enhancing drug sensitivity through the IRF7/HMGCS1 pathway. These findings suggest potential therapeutic targets for improving AML treatment outcomes.

Keywords

Acute myeloid leukemia; BCL7A; Drug resistance; HMGCS1; IRF7.

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