ArticleThe Journal of clinical investigation2018
Hypoxia-induced upregulation of BMX kinase mediates therapeutic resistance in acute myeloid leukemia.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 38 citations in OpenAlex.
- Targeting the BMX in cancer: molecular mechanisms and emerging therapeutic strategies.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Riding toward Selectivity: Optimization of Covalent 7-Azaindole-Based BMX Kinase Inhibitors.Journal of medicinal chemistry · 2026Article
- BMX inhibition overcomes small cell lung cancer chemoresistance by stabilizing E2F1 via ERK1/2-Cyclin D1/CDK4/6 axis.Signal transduction and targeted therapy · 2026Article
- Multiomic analysis of clonal development reveals new regulators of leukemic cell growth.Genes & development · 2026Article
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- Drug-Drug Interaction Liabilities with BTK Inhibitor TL-895.Cancer research communications · 2025Article
- Strategic innovations: Tackling challenges of immunotherapy in acute myeloid leukemia.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Overcoming the sorafenib resistance mechanism in FLT3-mutated acute myeloid leukemia: molecular basis and new targets.Frontiers in oncology · 2025Review
- Role of the CDKL1-SOX11 signaling axis in acute kidney injury.American journal of physiology. Renal physiology · 2024Article
- DERL2 (derlin 2) stabilizes BAG6 (BAG cochaperone 6) in chemotherapy resistance of cholangiocarcinoma.Journal of physiology and biochemistry · 2024Article
- Venetoclax Overcomes Sorafenib Resistance in Acute Myeloid Leukemia by Targeting BCL2.Biology · 2023Article
- Zinc finger protein 24-dependent transcription factor SOX9 up-regulation protects tubular epithelial cells during acute kidney injury.Kidney international · 2023Article
- BMX kinase mediates gilteritinib resistance in FLT3-mutated AML through microenvironmental factors.Blood advances · 2022Article
- Put in a "CaCells · 2022Review
- Article
- Article
- USP29-mediated HIF1α stabilization is associated with Sorafenib resistance of hepatocellular carcinoma cells by upregulating glycolysis.Oncogenesis · 2021Article
- Leukemia stem cell-bone marrow microenvironment interplay in acute myeloid leukemia development.Experimental hematology & oncology · 2021Review
- Benefit of a single simulated hypobaric hypoxia in healthy mice performance and analysis of mitochondria-related gene changes.Scientific reports · 2021Article
- SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells.The Journal of biological chemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Oncogenic addiction to the Fms-like tyrosine kinase 3 (FLT3) is a hallmark of acute myeloid leukemia (AML) that harbors the FLT3-internal tandem duplication (FLT3-ITD) mutation. While FLT3 inhibitors like sorafenib show initial therapeutic efficacy, resistance rapidly develops through mechanisms that are incompletely understood. Here, we used RNA-Seq-based analysis of patient leukemic cells and found that upregulation of the Tec family kinase BMX occurs during sorafenib resistance. This upregulation was recapitulated in an in vivo murine FLT3-ITD-positive (FLT3-ITD+) model of sorafenib resistance. Mechanistically, the antiangiogenic effects of sorafenib led to increased bone marrow hypoxia, which contributed to HIF-dependent BMX upregulation. In in vitro experiments, hypoxia-dependent BMX upregulation was observed in both AML and non-AML cell lines. Functional studies in human FLT3-ITD+ cell lines showed that BMX is part of a compensatory signaling mechanism that promotes AML cell survival during FLT3 inhibition. Taken together, our results demonstrate that hypoxia-dependent upregulation of BMX contributes to therapeutic resistance through a compensatory prosurvival signaling mechanism. These results also reveal the role of off-target drug effects on tumor microenvironment and development of acquired drug resistance. We propose that the bone marrow niche can be altered by anticancer therapeutics, resulting in drug resistance through cell-nonautonomous microenvironment-dependent effects.
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.