ArticleBlood2021
A novel and highly effective mitochondrial uncoupling drug in T-cell leukemia.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 17 citations in OpenAlex.
- Identification of immune reconstitution and hematopoiesis restoration by scRNA-seq in bone marrow of multiple myeloma patients treated with high-dose melphalan following auto-HSCT.Cancer biology & medicine · 2026Article
- Mitochondrial dysfunction in hypertension: mechanistic pathways and therapeutic implications.Functional & integrative genomics · 2026Review
- PTEN-loss confers dependence on the guanylate synthesis enzyme IMPDH in T-cell acute lymphoblastic leukemia.bioRxiv : the preprint server for biology · 2025Article
- A dietary pan-amino acid dropout screenbioRxiv : the preprint server for biology · 2025Article
- Canagliflozin synergises with serine restriction mediating anti-leukaemic effects in T-cell acute lymphoblastic leukaemia.Molecular metabolism · 2025Article
- A feedforward loop between ACLY and MYC supports T-ALL progression in vivo.Blood neoplasia · 2025Article
- Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress.Blood · 2023Article
- Salicylanilides and Their Anticancer Properties.International journal of molecular sciences · 2023Review
- A Therapeutically Targetable NOTCH1-SIRT1-KAT7 Axis in T-cell Leukemia.Blood cancer discovery · 2023Article
- Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia.Nature communications · 2022Article
- RAS activation induces synthetic lethality of MEK inhibition with mitochondrial oxidative metabolism in acute myeloid leukemia.Leukemia · 2022Article
- One Omics Approach Does Not Rule Them All: The Metabolome and the Epigenome Join Forces in Haematological Malignancies.Epigenomes · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy. Despite recent advances in treatments with intensified chemotherapy regimens, relapse rates and associated morbidities remain high. In this context, metabolic dependencies have emerged as a druggable opportunity for the treatment of leukemia. Here, we tested the antileukemic effects of MB1-47, a newly developed mitochondrial uncoupling compound. MB1-47 treatment in T-ALL cells robustly inhibited cell proliferation via both cytostatic and cytotoxic effects as a result of compromised mitochondrial energy and metabolite depletion, which severely impaired nucleotide biosynthesis. Mechanistically, acute treatment with MB1-47 in primary leukemias promoted adenosine monophosphate-activated serine/threonine protein kinase (AMPK) activation and downregulation of mammalian target of rapamycin (mTOR) signaling, stalling anabolic pathways that support leukemic cell survival. Indeed, MB1-47 treatment in mice harboring either murine NOTCH1-induced primary leukemias or human T-ALL patient-derived xenografts (PDXs) led to potent antileukemic effects with a significant extension in survival without overlapping toxicities. Overall, our findings demonstrate a critical role for mitochondrial oxidative phosphorylation in T-ALL and uncover MB1-47-driven mitochondrial uncoupling as a novel therapeutic strategy for the treatment of this disease.
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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 Socratic graph.