ArticleLeukemia2012
MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-activated MCL-1 induction and modulation of MCL-1/BIM complex.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 89 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
89 citing papers in PubMed, 140 citations in OpenAlex.
- CXCR4 chemokine receptor signaling induces apoptosis in acute myeloid leukemia cells via regulation of the Bcl-2 family members Bcl-XL, Noxa, and Bak.The Journal of biological chemistry · 2013Trial
- Targeting MCL-1 and MAPK overcomes venetoclax resistance in FLT3-ITD-positive AML cells harbouring activating PTPN11 (SHP-2) mutations.British journal of haematology · 2026Article
- ABT‑737 increases cisplatin sensitivity through the ROS‑ASK1‑JNK MAPK signaling axis in human ovarian cancer cisplatin‑resistant A2780/DDP cells.Oncology reports · 2024Article
- Article
- BCL-2 inhibitors in hematological malignancies: biomarkers that predict response and management strategies.Frontiers in oncology · 2024Review
- Recent Updates in Venetoclax Combination Therapies in Pediatric Hematological Malignancies.International journal of molecular sciences · 2023Review
- Co-targeting BCL-XL and BCL-2 by PROTAC 753B eliminates leukemia cells and enhances efficacy of chemotherapy by targeting senescent cells.Haematologica · 2023Article
- Augmenting Venetoclax Activity Through Signal Transduction in AML.Journal of cellular signaling · 2023Article
- An integrative systems biology approach to overcome venetoclax resistance in acute myeloid leukemia.PLoS computational biology · 2022Article
- Progress in understanding the mechanisms of resistance to BCL-2 inhibitors.Experimental hematology & oncology · 2022Review
- Adapted to Survive: Targeting Cancer Cells with BH3 Mimetics.Cancer discovery · 2022Review
- Synergistic efficacy of homoharringtonine and venetoclax on acute myeloid leukemia cells and the underlying mechanisms.Annals of translational medicine · 2022Article
- Targeting Apoptosis in Cancer.Current oncology reports · 2022Review
- ABT199/venetoclax potentiates the cytotoxicity of alkylating agents and fludarabine in acute myeloid leukemia cells.Oncotarget · 2022Article
- BH3-only protein expression determines hepatocellular carcinoma response to sorafenib-based treatment.Cell death & disease · 2021Article
- Bayesian multi-source regression and monocyte-associated gene expression predict BCL-2 inhibitor resistance in acute myeloid leukemia.NPJ precision oncology · 2021Article
- Targeting epigenetic mechanisms to overcome venetoclax resistance.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Arsenic trioxide synergistically promotes the antileukaemic activity of venetoclax by downregulating Mcl-1 in acute myeloid leukaemia cells.Experimental hematology & oncology · 2021Article
- Combinatorial Strategies to Target Molecular and Signaling Pathways to Disarm Cancer Stem Cells.Frontiers in oncology · 2021Review
- Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.Signal transduction and targeted therapy · 2020Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retraction · 2024-07-18Concerns/Issues about Data · Duplication of/in Image · Investigation by Journal/Publisher · Objections by Author(s) · Unreliable Data · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Recently, strategies for acute myeloid leukemia (AML) therapy have been developed that target anti-apoptotic BCL2 family members using BH3-mimetic drugs such as ABT-737. Though effective against BCL2 and BCL-X(L), ABT-737 poorly inhibits MCL-1. Here we report that, unexpectedly, ABT-737 induces activation of the extracellular receptor activated kinase and induction of MCL-1 in AML cells. MEK inhibitors such as PD0325901 and CI-1040 have been used successfully to suppress MCL-1. We report that PD0325901 blocked ABT-737-induced MCL-1 expression, and when combined with ABT-737 resulted in potent synergistic killing of AML-derived cell lines, primary AML blast and CD34+38-123+ progenitor/stem cells. Finally, we tested the combination of ABT-737 and CI-1040 in a murine xenograft model using MOLM-13 human leukemia cells.Whereas control mice and CI-1040-treated mice exhibited progressive leukemia growth, ABT-737, and to a significantly greater extent, ABT-737+CI-1040 exerted major anti-leukemia activity. Collectively, results demonstrated unexpected anti-apoptotic interaction between the BCL2 family-targeted BH3-mimetic ABT-737 and mitogen-activated protein kinase signaling in AML cells: the BH3 mimetic is not only restrained in its activity by MCL-1, but also induces its expression. However, concomitant inhibition by BH3 mimetics and MEK inhibitors could abrogate this effect and may be developed into a novel and effective therapeutic strategy for patients with AML.
Indexed as
Identifiers
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.