ArticleLeukemia2008
Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway.
Article in Leukemia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- Clinical Benefits and Safety of FMS-Like Tyrosine Kinase 3 Inhibitors in Various Treatment Stages of Acute Myeloid Leukemia: A Systematic Review, Meta-Analysis, and Network Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Trial
- Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010Trial
- Stretching a doublet into a triplet for FLT3 AML.Blood advances · 2026Article
- Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia.Nature reviews. Clinical oncology · 2025Review
- 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
- Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort.Investigational new drugs · 2024Article
- Inhibition of Dickkopf-1 enhances the anti-tumor efficacy of sorafenib via inhibition of the PI3K/Akt and Wnt/β-catenin pathways in hepatocellular carcinoma.Cell communication and signaling : CCS · 2023Article
- Review
- FLT3 inhibitors for acute myeloid leukemia: successes, defeats, and emerging paradigms.RSC medicinal chemistry · 2022Review
- Artesunate improves venetoclax plus cytarabine AML cell targeting by regulating the Noxa/Bim/Mcl-1/p-Chk1 axis.Cell death & disease · 2022Article
- A review of FLT3 inhibitors in acute myeloid leukemia.Blood reviews · 2022Review
- Dual-Targeted Therapy Circumvents Non-Genetic Drug Resistance to Targeted Therapy.Frontiers in oncology · 2022Review
- BCL-2 Inhibitor ABT-737 Effectively Targets Leukemia-Initiating Cells with Differential Regulation of Relevant Genes Leading to Extended Survival in a NRAS/BCL-2 Mouse Model of High Risk-Myelodysplastic Syndrome.International journal of molecular sciences · 2021Article
- FLT3 tyrosine kinase inhibitors synergize with BCL-2 inhibition to eliminate FLT3/ITD acute leukemia cells through BIM activation.Signal transduction and targeted therapy · 2021Article
- The application of BH3 mimetics in myeloid leukemias.Cell death & disease · 2021Review
- The role of cell signaling in the crosstalk between autophagy and apoptosis in the regulation of tumor cell survival in response to sorafenib and neratinib.Seminars in cancer biology · 2020Review
- Design and synthesis of phthalazine-based compounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Targeting Tyrosine Kinases in Acute Myeloid Leukemia: Why, Who and How?International journal of molecular sciences · 2019Review
- Blockade of ERK1/2 by U0126 alleviates uric acid-induced EMT and tubular cell injury in rats with hyperuricemic nephropathy.American journal of physiology. Renal physiology · 2019Article
32 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
9 authors at 2 institutions in 1 country.
Funding
Abstract
Raf/MEK/Erk signaling is activated in the majority of acute myeloid leukemias (AMLs), providing rationale for targeting this pathway with therapeutic intent. We investigated growth-inhibitory and proapoptotic effects of sorafenib in AML. Our studies demonstrated that sorafenib significantly inhibited the phosphorylation levels of Raf downstream target proteins MEK1/2 and Erk, induced apoptosis and inhibited colony formation in AML cell lines and in primary AML samples. Mechanistically, treatment with sorafenib resulted in upregulation of proapoptotic Bim, accompanied by an increase in Bad, Bax and Bak protein levels and decreased Mcl-1, X-linked inhibitor of apoptosis and surviving levels, which mainly led to the activation of the intrinsic apoptotic pathway. Silencing of Bim protein expression significantly abrogated sorafenib-induced apoptosis, suggesting a critical function of Bim in the activation of the intrinsic mitochondrial pathway induced by sorafenib. Importantly, sorafenib also modulated phospho-Erk, Bim, Bax and Mcl-1 levels in samples procured from patients in an ongoing Phase I clinical trial of sorafenib in AML. Combination of sorafenib with cytarabine or the novel small molecule Bcl-2 inhibitor ABT-737 synergistically induced cell death in AML cell lines. Our results strongly suggest potential activity of sorafenib as a novel mechanism-based therapeutic agent in 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.