ArticleLeukemia2015
Dual PI3K/mTOR inhibition shows antileukemic activity in MLL-rearranged acute myeloid leukemia.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- Revisiting retinoic acid in AML therapy: mechanisms of action and rational combination strategies.British journal of cancer · 2026Review
- Exploiting an epigenetic resistance mechanism to PI3-kinase inhibition in leukemic stem cells.Leukemia · 2026Article
- Age-specific mutation profiles and their prognostic implications in pediatricHaematologica · 2026Article
- Enhanced Anti-Leukemic Activity of Platinum Lamivudine Compared To Lamivudine Through Differential Gene Regulation and DNA Groove Binding.Cell biochemistry and biophysics · 2025Article
- Inhibition of PI3K/AKT/mTOR signaling enhances autophagy in HL-60 acute myeloid leukemia cells: An integrative bioinformatic and in vitro study.Biochemistry and biophysics reports · 2025Article
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- Identification of alkynyl nicotinamide HSN748 as a RET solvent-front mutant inhibitor with intracranial efficacy.RSC medicinal chemistry · 2025Article
- Comparative performance of scFv-based anti-BCMA CAR formats for improved T cell therapy in multiple myeloma.Cancer immunology, immunotherapy : CII · 2024Article
- Efficient Chimeric Antigen Receptor T-Cell Generation Starting with Leukoreduction System Chambers of Thrombocyte Apheresis Sets.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2024Article
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- Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia.Nature biotechnology · 2023Article
- Programmable multispecific DNA-origami-based T-cell engagers.Nature nanotechnology · 2023Article
- Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.Hematology reports · 2023Review
- Major immunophenotypic abnormalities in patients with primary adrenal insufficiency of different etiology.Frontiers in immunology · 2023Article
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- Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.Signal transduction and targeted therapy · 2021Review
- Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review.International journal of molecular sciences · 2021Review
- Anlotinib suppresses MLL-rearranged acute myeloid leukemia cell growth by inhibiting SETD1A/AKT-mediated DNA damage response.American journal of translational research · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In acute myeloid leukemia (AML), several signaling pathways such as the phosphatidylinositol-3-kinase/AKT and the mammalian target of rapamycin (PI3K/AKT/mTOR) pathway are deregulated and constitutively activated as a consequence of genetic and cytogenetic abnormalities. We tested the effectiveness of PI3K/AKT/mTOR-targeting therapies and tried to identify alterations that associate with treatment sensitivity. By analyzing primary samples and cell lines, we observed a wide range of cytotoxic activity for inhibition of AKT (MK-2206), mTORC1 (rapamycin) and PI3K/mTORC1/2 (BEZ-235) with a high sensitivity of cells carrying an MLL rearrangement. In vivo PI3K/mTOR inhibition delayed tumor progression, reduced tumor load and prolonged survival in an MLL-AF9(+)/FLT3-ITD(+) xenograft mouse model. By performing targeted amplicon sequencing in 38 MLL-AF9(+) and 125 cytogenetically normal AML patient samples, we found a high additional mutation rate for genes involved in growth factor signaling in 79% of all MLL-AF9(+) samples, which could lead to a possible benefit of this cohort. PI3K/mTOR inhibition for 24 h led to the cross-activation of the ERK pathway. Further in vitro studies combining PI3K/mTOR and ERK pathway inhibition revealed highly synergistic effects in apoptosis assays. Our data implicate a possible therapeutic benefit of PI3K/mTOR inhibition in the MLL-mutated subgroup. Inhibiting rescue pathways could improve the therapeutic efficacy of PI3K-targeted therapies in AML.
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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.