Trial reportThe Journal of clinical investigation2013
Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors.
Trial report in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 142 citations in OpenAlex.
- Overcoming Radiation Resistance: Ferroptosis Induction to Sensitize Solid Tumors to Radiation Therapy.Cancer medicine · 2026Review
- Evaluation of Darifenacin for T-Cell Acute Lymphoblastic Leukemia: Selective Targeting of the Non-Neuronal Cholinergic System and Lysosomal Cathepsins.International journal of molecular sciences · 2026Article
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Machine learning-based integration develops a novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in acute myeloid leukemia.Discover oncology · 2026Article
- CLN7 suppression induces apoptosis via mTOR-regulated and chaperone-mediated autophagy in myeloid leukemia cells.Cell death & disease · 2026Article
- One-Pot Gateway to Quinazoline-Thiohydantoin Fused Scaffolds and Discovery of Their Antileukemic Activity.JACS Au · 2026Article
- Targeting Glycolysis with 2-Deoxy-D-Glucose and Lysosomal Integrity with L-Leucyl-L-Leucine Methyl Ester as Antimelanoma Strategy.Pharmaceutics · 2025Article
- Article
- Endolysosome-targeted nanoparticle delivery of antiviral therapy for coronavirus infections.Life science alliance · 2025Article
- Article
- Lysosomal cation channel TRPML1 suppression sensitizes acute myeloid leukemia cells to chemotherapeutics by inhibiting autophagy.Molecular and cellular biochemistry · 2025Article
- Lysosome targeted therapies in hematological malignancies.Frontiers in oncology · 2025Review
- Deregulation of New Cell Death Mechanisms in Leukemia.Cancers · 2024Review
- Cationic amphiphilic drugs induce accumulation of cytolytic lysoglycerophospholipids in the lysosomes of cancer cells and block their recycling into common membrane glycerophospholipids.Molecular biology of the cell · 2024Article
- Hexamethylene amiloride synergizes with venetoclax to induce lysosome-dependent cell death in acute myeloid leukemia.iScience · 2024Article
- Progress in the study of mefloquine as an antibiotic adjuvant for combination bacterial inhibition treatment.Frontiers in cellular and infection microbiology · 2024Review
- Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.Mini reviews in medicinal chemistry · 2024Review
- Associations of serum cystatin C concentrations with total mortality and mortality of 12 site-specific cancers.Frontiers in molecular biosciences · 2024Article
- Identification of PPT1 as a lysosomal core gene with prognostic value in hepatocellular carcinoma.Bioscience reports · 2023Article
- Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
38 authors at 6 institutions in 5 countries.
Funding
Abstract
Despite efforts to understand and treat acute myeloid leukemia (AML), there remains a need for more comprehensive therapies to prevent AML-associated relapses. To identify new therapeutic strategies for AML, we screened a library of on- and off-patent drugs and identified the antimalarial agent mefloquine as a compound that selectively kills AML cells and AML stem cells in a panel of leukemia cell lines and in mice. Using a yeast genome-wide functional screen for mefloquine sensitizers, we identified genes associated with the yeast vacuole, the homolog of the mammalian lysosome. Consistent with this, we determined that mefloquine disrupts lysosomes, directly permeabilizes the lysosome membrane, and releases cathepsins into the cytosol. Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. Highlighting a potential therapeutic rationale for this strategy, leukemic cells had significantly larger lysosomes compared with normal cells, and leukemia-initiating cells overexpressed lysosomal biogenesis genes. These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML.
Indexed as
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What OpenQuestion holds
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.