ArticleSignal transduction and targeted therapy
Inhibition of Mcl-1 enhances cell death induced by the Bcl-2-selective inhibitor ABT-199 in acute myeloid leukemia cells.
Article in Signal transduction and targeted therapy. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 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
78 citing papers in PubMed, 126 citations in OpenAlex.
- FLA-IDA salvage chemotherapy combined with a seven-day course of venetoclax (FLAVIDA) in patients with relapsed/refractory acute leukaemia.British journal of haematology · 2020Trial
- A Phase I/II Trial of MEC (Mitoxantrone, Etoposide, Cytarabine) in Combination with Ixazomib for Relapsed Refractory Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- G3BP2 confers venetoclax resistance by stabilizing ELF1-mediated MCL1 transcription in acute myeloid leukemia.Leukemia · 2026Article
- Synergistic targeting of eIF4A-mediated translation initiation and apoptosis in acute myeloid leukemia.Blood neoplasia · 2026Article
- 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
- NaCells · 2025Article
- Targeting Bcl-2 with Indole Scaffolds: Emerging Drug Design Strategies for Cancer Treatment.Mini reviews in medicinal chemistry · 2025Review
- Synergistic cytotoxicity of decitabine and YM155 in leukemia cells through upregulation of SLC35F2 and suppression of MCL1 and survivin expression.Apoptosis : an international journal on programmed cell death · 2024Article
- Inhibition of NRF2 enhances the acute myeloid leukemia cell death induced by venetoclax via the ferroptosis pathway.Cell death discovery · 2024Article
- Venetoclax Combined with Intensive Chemotherapy: A New Hope for Refractory and/or Relapsed Acute Myeloid Leukemia?Journal of clinical medicine · 2024Review
- Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy.IUBMB life · 2024Review
- Impact of p53-associated acute myeloid leukemia hallmarks on metabolism and the immune environment.Frontiers in pharmacology · 2024Review
- KS18, a Mcl-1 inhibitor, improves the effectiveness of bortezomib and overcomes resistance in refractory multiple myeloma by triggering intrinsic apoptosis.Frontiers in pharmacology · 2024Article
- The Effects of ABT-199 and Dihydroartemisinin Combination on Cell Growth and Apoptosis in Human U937 and KG-1 Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Tetrazole and acylsulfonamide bioisosteric replacements of the carboxylic acid in a dual MCL-1/BCL-xRSC advances · 2023Article
- Venetoclax, alone and in combination with the BH3 mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice.Cell reports. Medicine · 2023Article
- Osimertinib is a dual inhibitor of hepatocellular carcinoma and angiogenesis in an EGFR-independent manner, and synergizes with venetoclax.Journal of cancer research and clinical oncology · 2023Article
- A novel Mcl-1 inhibitor synergizes with venetoclax to induce apoptosis in cancer cells.Molecular medicine (Cambridge, Mass.) · 2023Article
- Halogenated boroxine increases propensity to apoptosis in leukemia (UT-7) but not non-tumor cells in vitro.FEBS open bio · 2023Article
- Targeting anti-apoptotic pathways eliminates senescent melanocytes and leads to nevi regression.Nature communications · 2022Article
18 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
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Acute myeloid leukemia (AML) is a serious disease. The 5-year survival rates remain frustratingly low (65% for children and 26% for adults). Resistance to frontline chemotherapy (usually cytarabine) often develops; therefore a new treatment modality is needed. Bcl-2 family proteins play an important role in balancing cell survival and apoptosis. The antiapoptotic Bcl-2 family proteins have been found to be dysregulated in AML. ABT-199, a BH3 mimetic, was developed to target antiapoptotic protein Bcl-2. Although ABT-199 has demonstrated promising results, resistance occurs. Previous studies in AML show that ABT-199 alone decreases the association of proapoptotic protein Bim with Bcl-2, but this is compensated by increased association of Bim with prosurvival protein Mcl-1, stabilizing Mcl-1, resulting in resistance to ABT-199. In this study, we investigated the antileukemic activity of the Mcl-1-selective inhibitor A-1210477 in combination with ABT-199 in AML cells. We found that A-1210477 synergistically induced apoptosis with ABT-199 in AML cell lines and primary patient samples. The synergistic induction of apoptosis was decreased upon Bak, Bax and Bim knockdown. While A-1210477 treatment alone also increased Mcl-1 protein levels, combination with ABT-199 reduced binding of Bim to Mcl-1. Our results demonstrate that sequestration of Bim by Mcl-1, a mechanism of ABT-199 resistance, can be abrogated by combined treatment with the Mcl-1 inhibitor A-1201477.
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.