ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Sorafenib Inhibition of Mcl-1 Accelerates ATRA-Induced Apoptosis in Differentiation-Responsive AML Cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 46 citations in OpenAlex.
- Revisiting retinoic acid in AML therapy: mechanisms of action and rational combination strategies.British journal of cancer · 2026Review
- mTOR inhibition promotes ATRA-induced cancer cell differentiation by overcoming a metabolic hyperactive state.Journal of translational medicine · 2026Article
- Reawakening Differentiation Therapy in Acute Myeloid Leukemia: A Comprehensive Review of ATRA-Based Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- Overexpression of miR-99a promoted expansion and suppressed differentiation of hematopoietic stem/progenitor cells.Scientific reports · 2025Article
- Retrospective analysis of sorafenib combined with interferon α-1b, interleukin-2, and thalidomide as maintenance therapy in FLT3-ITD-positive acute myeloid leukemia.Frontiers in oncology · 2025Article
- All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia.Frontiers in pharmacology · 2024Review
- Synergistic Action of MCL-1 Inhibitor with BCL-2/BCL-XL or MAPK Pathway Inhibitors Enhances Acute Myeloid Leukemia Cell Apoptosis and Differentiation.International journal of molecular sciences · 2023Article
- Artesunate improves venetoclax plus cytarabine AML cell targeting by regulating the Noxa/Bim/Mcl-1/p-Chk1 axis.Cell death & disease · 2022Article
- Skp2 stabilizes Mcl-1 and confers radioresistance in colorectal cancer.Cell death & disease · 2022Article
- Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas.International journal of molecular sciences · 2021Review
- Arsenic trioxide synergistically promotes the antileukaemic activity of venetoclax by downregulating Mcl-1 in acute myeloid leukaemia cells.Experimental hematology & oncology · 2021Article
- Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax.Blood advances · 2021Article
- AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma.Blood advances · 2020Article
- DDX5-targeting fully human monoclonal autoantibody inhibits proliferation and promotes differentiation of acute promyelocytic leukemia cells by increasing ROS production.Cell death & disease · 2020Article
- Autophagy as a Potential Therapy for Malignant Glioma.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Saga of Mcl-1: regulation from transcription to degradation.Cell death and differentiation · 2020Review
- Notopterol-induced apoptosis and differentiation in human acute myeloid leukemia HL-60 cells.Drug design, development and therapy · 2019Article
- A triple drug combination as a novel anti-glioma therapy?Oncotarget · 2018Article
- Tyrosine Kinase Inhibitors Increase MCL1 Degradation and in Combination with BCLXL/BCL2 Inhibitors Drive Prostate Cancer Apoptosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Dual Inhibition of Bcl-2/Bcl-xL and XPO1 is synthetically lethal in glioblastoma model systems.Scientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeAll trans-retinoic acid (ATRA) is successful in treating acute promyelocytic leukemia (APL) by inducing terminal differentiation-mediated cell death, but it has limited activity in non-APL acute myeloid leukemia (AML). We aim to improve ATRA therapy of AML by enhancing apoptosis through repression of the antiapoptotic proteins Bcl-2 and Mcl-1. EXPERIMENTAL
designAPL and AML cell lines, as well as primary AML samples, were used to explore the mechanisms regulating differentiation and apoptosis during ATRA treatment. Stable transfection and gene silencing with siRNA were used to identify the key factors that inhibit apoptosis during induction of differentiation and drugs that accelerate apoptosis.
resultsIn differentiation-responsive AML cells, ATRA treatment induces long-lasting repression of Bcl-2 while first upmodulating and then reducing the Mcl-1 level. The Mcl-1 level appears to serve as a gatekeeper between differentiation and apoptosis. During differentiation induction, activation of MEK/ERK and PI3K/Akt pathways by ATRA leads to activation of p90RSK and inactivation of glycogen synthase kinase 3β (GSK3β), which increase Mcl-1 levels by increasing its translation and stability. Sorafenib blocks ATRA-induced Mcl-1 increase by reversing p90RSK activation and GSK3β inactivation, maintains the repressed Bcl-2 level, and enhances ATRA induced apoptosis in non-APL AML cell lines and in primary AML cells.
conclusionsInhibition of Mcl-1 is required for apoptosis induction in ATRA differentiation-responsive AML cells. ATRA and sorafenib can be developed as a novel drug combination therapy for AML patients because this drug combination augments apoptosis by inhibiting Bcl-2 and Mcl-1.
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.