ArticleBiomarker research2022
Therapeutic targeting of PFKFB3 and PFKFB4 in multiple myeloma cells under hypoxic conditions.
Article in Biomarker research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- [Progress in metabolomics of multiple myeloma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Review
- USP5 motivates immunosuppressive microenvironment in multiple myeloma by activating STAT2-PFKFB4-mediated glycolysis.Cancer immunology, immunotherapy : CII · 2025Article
- Targeting macrophage polarization by inhibiting Pim2 alleviates inflammatory arthritis via metabolic reprogramming.Cellular & molecular immunology · 2025Article
- Glutaminase 1 plays critical roles in myelodysplastic syndrome and acute myeloid leukemia cells.Cancer biomarkers : section A of Disease markers · 2024Article
- Airborne fine particulate matter exposure induces transcriptomic alterations resembling asthmatic signatures: insights from integrated omics analysis.Environmental epigenetics · 2024Article
- Effect of asciminib and vitamin K2 on Abelson tyrosine-kinase-inhibitor-resistant chronic myelogenous leukemia cells.BMC cancer · 2023Article
- Metabolic changes underlying drug resistance in the multiple myeloma tumor microenvironment.Frontiers in oncology · 2023Article
- A novel glycolysis-related gene signature for predicting the prognosis of multiple myeloma.Frontiers in cell and developmental biology · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The treatment of multiple myeloma (MM) patients has been dramatically changed by the introduction of new agents; however, many patients relapse. Hypoxia is a critical component of the bone-marrow microenvironment. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) is responsible for maintaining cellular levels of fructose-2,6-bisphosphate, which regulates glycolysis. We found that the gene expressions of PFKFB3 and PFKFB4 were elevated under hypoxic conditions. Treatments with the PFKFB3 inhibitor, PFK158, and PFKFB4 inhibitor, 5MPN, were found to inhibit the growth of myeloma cells. The combined treatment of myeloma cells with carfilzomib and PFK158 or 5MPN was more cytotoxic than either drug alone. Caspase 3/7 activity and cellular cytotoxicity were also increased. In addition, the combined treatment was effective in the bortezomib-resistant cell line. Our data also suggest that administration of PFKFB3 and PFKFB4 inhibitors may be a powerful strategy against myeloma cells and to enhance the cytotoxic effects of proteasome inhibitors in hypoxic conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.