ArticleCancer science2021
Pyruvate dehydrogenase kinase 4-mediated metabolic reprogramming is involved in rituximab resistance in diffuse large B-cell lymphoma by affecting the expression of MS4A1/CD20.
Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Overcoming chemotherapy resistance in diffuse large B-cell lymphoma using multifunctional nanocarriers: current advances and clinical challenges.Discover nano · 2026Review
- PDK4 drives abdominal aortic aneurysm by promoting smooth muscle cell metabolic reprogramming and NLRP3-mediated pyroptosis.Nature communications · 2026Article
- Mechanisms of chemoresistance in diffuse large B‑cell lymphoma and novel therapeutic strategies (Review).International journal of oncology · 2026Review
- MPC2 Overexpression Drives Mitochondrial Oxidative Phosphorylation and Promotes Progression in Diffuse Large B-Cell Lymphoma.Biochemical genetics · 2026Article
- Amino Acid Metabolism-Related Gene Kynureninase (KYNU) as a Prognostic Predictor and Regulator of Diffuse Large B-Cell Lymphoma.Biochemical genetics · 2026Article
- P300 enhances glycolysis and dox resistance in DLBCL by upregulating HK2 expression through histone lactylation.BMC cancer · 2026Article
- Molecular mechanisms of RACK1-driven metastasis in pancreatic ductal adenocarcinoma revealed by single-cell RNA sequencing.Discover oncology · 2025Article
- Expanding the potential of antibody-drug conjugates in gastrointestinal malignancies: beyond HER2 targets.ESMO gastrointestinal oncology · 2025Review
- Impact of immune cell metabolism on membranous nephropathy and prospective therapy.Communications biology · 2025Review
- Macrophage Membrane-Coated Liposomes Delivering Vonoprazan Disrupt Mitochondrial Oxidative Phosphorylation in Diffuse Large B-Cell Lymphoma.International journal of nanomedicine · 2025Article
- Unveiling the PDK4-centered rituximab-resistant mechanism in DLBCL: the potential of the "Smart" exosome nanoparticle therapy.Molecular cancer · 2024Article
- Article
- Antibody-drug conjugates come of age in oncology.Nature reviews. Drug discovery · 2023Review
- α-KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis.Cell death discovery · 2023Article
- RETRACTED: TRIM10 Is Downregulated in Acute Myeloid Leukemia and Plays a Tumor Suppressive Role via Regulating NF-κB Pathway.Cancers · 2023Article
- Role of the membrane-spanning 4A gene family in lung adenocarcinoma.Frontiers in genetics · 2023Article
- Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next?Cancers · 2022Review
- Pyruvate dehydrogenase kinase 4-mediated metabolic reprogramming is involved in rituximab resistance in diffuse large B-cell lymphoma by affecting the expression of MS4A1/CD20.Cancer science · 2021Article
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Authors and funding
8 authors at 4 institutions in 1 country.
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Abstract
Diffuse large B cell lymphoma (DLBCL) heterogeneity promotes recurrence and anti-CD20-based therapeutic resistance. Previous studies have shown that downregulation of MS4A1/CD20 expression after chemoimmunotherapy with rituximab leads to rituximab resistance. However, the mechanisms of CD20 loss remain unknown. We identified that pyruvate dehydrogenase kinase 4 (PDK4) is markedly elevated in DLBCL cells derived from both patients and cell lines with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) resistance. We found that overexpression of PDK4 in DLBCL cells resulted in cell proliferation and resistance to rituximab in vitro and in vivo. Furthermore, loss of PDK4 expression or treatment with the PDK4 inhibitor dichloroacetate was able to significantly increase rituximab-induced cell apoptosis in DLBCL cells. Further studies suggested PDK4 mediates a metabolic shift, in that the main energy source was changed from oxidative phosphorylation to glycolysis, and the metabolic changes could play an important role in rituximab resistance. Importantly, by knocking down or overexpressing PDK4 in DLBCL cells, we showed that PDK4 has a negative regulation effect on MS4A1/CD20 expression. Collectively, this is the first study showing that targeting PDK4 has the potential to overcome rituximab resistance in DLBCL.
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