ArticleAutophagy2017
Autophagy is dispensable for Kmt2a/Mll-Mllt3/Af9 AML maintenance and anti-leukemic effect of chloroquine.
Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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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
29 citing papers in PubMed, 47 citations in OpenAlex.
- Circ-RERE promotes autophagy and immune escape in acute myeloid leukemia involving the miR-128-3p/ZEB1/PD-L1 axis.Clinics (Sao Paulo, Brazil) · 2026Article
- The multiplex crosstalk between non-coding RNAs, programmed cell death and related mechanisms: a dynamic duo in hematological malignancies.Cancer cell international · 2025Review
- Interplay between LncRNAs and autophagy-related pathways in leukemia: mechanisms and clinical implications.Medical oncology (Northwood, London, England) · 2025Review
- Current Understanding of the Role of Autophagy in the Treatment of Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Galectin-9 has non-apoptotic cytotoxic activity toward acute myeloid leukemia independent of cytarabine resistance.Cell death discovery · 2023Article
- Review
- Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia.Journal of cellular and molecular medicine · 2023Article
- Article
- The dual role of autophagy in acute myeloid leukemia.Journal of hematology & oncology · 2022Review
- LAMP-5 is an essential inflammatory-signaling regulator and novel immunotherapy target for mixed lineage leukemia-rearranged acute leukemia.Haematologica · 2022Article
- Approaches and Protocols to Analyze Autophagy and Its Role in Death of Apoptosis-Resistant Senescent Tumor Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Article
- Effects of the Autophagy-Inhibiting Agent Chloroquine on Acute Myeloid Leukemia Cells; Characterization of Patient Heterogeneity.Journal of personalized medicine · 2021Article
- Autophagy and Metabolism in Normal and Malignant Hematopoiesis.International journal of molecular sciences · 2021Review
- Inhibiting autophagy targets human leukemic stem cells and hypoxic AML blasts by disrupting mitochondrial homeostasis.Blood advances · 2021Article
- Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine.International journal of molecular sciences · 2021Article
- Article
- Overcoming Chemoresistance: Altering pH of Cellular Compartments by Chloroquine and Hydroxychloroquine.Frontiers in cell and developmental biology · 2021Review
- Acute lymphoblastic leukemia onset in a 3-year-old child with COVID-19.Pediatric blood & cancer · 2020Article
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Recently, macroautophagy/autophagy has emerged as a promising target in various types of solid tumor treatment. However, the impact of autophagy on acute myeloid leukemia (AML) maintenance and the validity of autophagy as a viable target in AML therapy remain unclear. Here we show that Kmt2a/Mll-Mllt3/Af9 AML (MA9-AML) cells have high autophagy flux compared with normal bone marrow cells, but autophagy-specific targeting, either through Rb1cc1-disruption to abolish autophagy initiation, or via Atg5-disruption to prevent phagophore (the autophagosome precursor) membrane elongation, does not affect the growth or survival of MA9-AML cells, either in vitro or in vivo. Mechanistically, neither Atg5 nor Rb1cc1 disruption impairs endolysosome formation or survival signaling pathways. The autophagy inhibitor chloroquine shows autophagy-independent anti-leukemic effects in vitro but has no efficacy in vivo likely due to limited achievable drug efficacy in blood. Further, vesicular exocytosis appears to mediate chloroquine resistance in AML cells, and exocytotic inhibition significantly enhances the anti-leukemic effect of chloroquine. Thus, chloroquine can induce leukemia cell death in vitro in an autophagy-independent manner but with inadequate efficacy in vivo, and vesicular exocytosis is a possible mechanism of chloroquine resistance in MA9-AML. This study also reveals that autophagy-specific targeting is unlikely to benefit MA9-AML therapy.
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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.