ArticleHaematologica2013
The synergism of MCL1 and glycolysis on pediatric acute lymphoblastic leukemia cell survival and prednisolone resistance.
Article in Haematologica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.International journal of molecular sciences · 2024Review
- The Effects of Resveratrol, Gallic Acid, and Piperine on the Expression of miR-17, miR-92b, miR-181a, miR-222, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA in Human Acute Myeloid Leukemia Cells and Their Roles in Apoptosis.Biochemical genetics · 2024Article
- Article
- Dasatinib overcomes glucocorticoid resistance in B-cell acute lymphoblastic leukemia.Nature communications · 2023Article
- The Role of Reprogrammed Glucose Metabolism in Cancer.Metabolites · 2023Review
- Plant-derived extracts and metabolic modulation in leukemia: a promising approach to overcome treatment resistance.Frontiers in molecular biosciences · 2023Review
- Early and Very Early GRIM19 and MCL1 Expression Are Correlated to Late Acquired Prednisolone Effects in a T-Cell Acute Leukemia Cell Line.Advances in experimental medicine and biology · 2021Article
- Vincristine and prednisone regulates cellular and exosomal miR-181a expression differently within the first time diagnosed and the relapsed leukemia B cells.Leukemia research reports · 2020Article
- Molecular mechanisms contributing to glucocorticoid resistance in lymphoid malignancies.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Combination of cabazitaxel and plicamycin induces cell death in drug resistant B-cell acute lymphoblastic leukemia.Leukemia research · 2018Article
- JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia.The Journal of experimental medicine · 2018Article
- The hypoxia signalling pathway in haematological malignancies.Oncotarget · 2017Review
- Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential.Cancer cell · 2016Article
- Hypoxia promotes chemoresistance in acute lymphoblastic leukemia cell lines by modulating death signaling pathways.BMC cancer · 2016Article
- miR-133 regulates Evi1 expression in AML cells as a potential therapeutic target.Scientific reports · 2016Article
- Mcl-1 downregulation leads to the heightened sensitivity exhibited by BCR-ABL positive ALL to induction of energy and ER-stress.Leukemia research · 2015Article
- Targeting mTOR/p70S6K/glycolysis signaling pathway restores glucocorticoid sensitivity to 4E-BP1 null Burkitt Lymphoma.BMC cancer · 2015Article
- Piperlongumine reverses doxorubicin resistance through the PI3K/Akt signaling pathway in K562/A02 human leukemia cells.Experimental and therapeutic medicine · 2015Article
- Towards personalized therapy in pediatric acute lymphoblastic leukemia: RAS mutations and prednisolone resistance.Haematologica · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
In vitro and in vivo resistance to prednisolone are predictive for an adverse prognosis in pediatric precursor B-acute lymphoblastic leukemia. Causes of resistance are still poorly understood. In this study, we observed that prednisolone exposure of prednisolone-sensitive patients' leukemic cells decreased anti-apoptotic MCL1 protein levels by 2.9-fold, while MCL1 protein expression in prednisolone-resistant leukemic patients' cells was unaffected (P<0.01). Locked nucleic acid oligonucleotides directed against MCL1 reduced MCL1 protein levels by 82±16% (P<0.05) in leukemic cells, decreased proliferation by 9-fold and sensitized to prednisolone up to 80.8-fold, compared to a non-silencing-control locked nucleic acid (P<0.05). Remarkably, we discovered that MCL1-silencing up-regulated the glucose consumption of leukemic cells by 2.5-fold (P<0.05), suggesting a potential rescue mechanism mediated by glycolysis. Targeting glycolysis by 2-deoxyglucose synergistically inhibited leukemic survival by 23.2-fold in MCL1-silenced cells (P<0.05). Moreover, 2-deoxyglucose and MCL1 locked nucleic acid concomitantly sensitized leukemic cells to prednisolone compared to MCL1 locked nucleic acid or 2-deoxyglucose alone (P<0.05). In conclusion, these results indicate the need to target both MCL1 and glycolysis simultaneously to inhibit leukemic survival and sensitize acute leukemia patients towards prednisolone.
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