ArticleLeukemia research2016
Synergistic cell death in FLT3-ITD positive acute myeloid leukemia by combined treatment with metformin and 6-benzylthioinosine.
Article in Leukemia research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Therapeutic potential of metformin-based combination therapy in acute myeloid leukemia.Discover oncology · 2025Review
- Targeting Glucose Transporter 1 (GLUT1) in Cancer: Molecular Mechanisms and Nanomedicine Applications.International journal of nanomedicine · 2025Review
- Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia.Current medical science · 2024Article
- Metformin synergizes with gilteritinib in treating FLT3-mutated leukemia via targeting PLK1 signaling.Cell reports. Medicine · 2024Article
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- The opportunities and challenges for nutritional intervention in childhood cancers.Frontiers in nutrition · 2023Review
- Pimozide and Imipramine Blue Exploit Mitochondrial Vulnerabilities and Reactive Oxygen Species to Cooperatively Target High Risk Acute Myeloid Leukemia.Antioxidants (Basel, Switzerland) · 2021Article
- Mitochondrial metabolism as a target for acute myeloid leukemia treatment.Cancer & metabolism · 2021Review
- Metformin - its anti-cancer effects in hematologic malignancies.Oncology reviews · 2021Article
- Power of two: combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Has Drug Repurposing Fulfilled its Promise in Acute Myeloid Leukaemia?Journal of clinical medicine · 2020Review
- The Role of Reactive Oxygen Species in Acute Myeloid Leukaemia.International journal of molecular sciences · 2019Review
- SIRT3 deacetylase activity confers chemoresistance in AML via regulation of mitochondrial oxidative phosphorylation.British journal of haematology · 2019Article
- Oxidative stress response induced by chemotherapy in leukemia treatment.Molecular and clinical oncology · 2018Article
- Metformin, an Anti-diabetic Drug to Target Leukemia.Frontiers in endocrinology · 2018Review
- Ordinary differential equations and Boolean networks in application to modelling of 6-mercaptopurine metabolism.Royal Society open science · 2017Article
- Review
- Drug Repurposing for the Treatment of Acute Myeloid Leukemia.Frontiers in medicine · 2017Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Current therapy for acute myeloid leukemia (AML) primarily includes high-dose cytotoxic chemotherapy with or without allogeneic stem cell transplantation. Targeting unique cellular metabolism of cancer cells is a potentially less toxic approach. Monotherapy with mitochondrial inhibitors like metformin have met with limited success since escape mechanisms such as increased glycolytic ATP production, especially in hyperglycemia, can overcome the metabolic blockade. As an alternative strategy for metformin therapy, we hypothesized that the combination of 6-benzylthioinosine (6-BT), a broad-spectrum metabolic inhibitor, and metformin could block this drug resistance mechanism. Metformin treatment alone resulted in significant suppression of ROS and mitochondrial respiration with increased glycolysis accompanied by modest cytotoxicity (10-25%). In contrast, 6-BT monotherapy resulted in inhibition of glucose uptake, decreased glycolysis, and decreased ATP with minimal changes in ROS and mitochondrial respiration. The combination of 6-BT with metformin resulted in significant cytotoxicity (60-70%) in monocytic AML cell lines and was associated with inhibition of FLT3-ITD activated STAT5 and reduced c-Myc and GLUT-1 expression. Therefore, although the anti-tumor and metabolic effects of metformin have been limited by the metabolic reprogramming within cells, the novel combination of 6-BT and metformin targets this bypass mechanism resulting in reduced glycolysis, STAT5 inhibition, and increased cell death.
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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.