Trial reportThe Journal of biological chemistry2014
Loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance in a B-lymphoblastic leukemia model.
Trial report in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 58 citations in OpenAlex.
- MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia.Blood · 2015Trial
- TBL1XR1 mutations promoted tumor progression in diffuse large B-cell lymphoma through impairing nature killer cytotoxicity via the MYC-CD47/PD-L1 axis.Molecular cancer · 2026Article
- A multiomic characterization of the leukemia cell line REH using short- and long-read sequencing.Life science alliance · 2024Article
- Central role of the mTORC1 pathway in glucocorticoid activity against B-ALL cells.Blood neoplasia · 2024Article
- Two decades of a protooncogene TBL1XR1: from a transcription modulator to cancer therapeutic target.Frontiers in oncology · 2024Review
- Article
- Emerging Epigenetic and Posttranslational Mechanisms Controlling Resistance to Glucocorticoids in Acute Lymphoblastic Leukemia.HemaSphere · 2023Review
- Steroid hormone signaling: multifaceted support of testicular function.Frontiers in cell and developmental biology · 2023Review
- Article
- Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML.Cell reports · 2022Article
- Nuclear Receptors in Energy Metabolism.Advances in experimental medicine and biology · 2022Article
- Drugs and Epigenetic Molecular Functions. A Pharmacological Data Scientometric Analysis.International journal of molecular sciences · 2021Article
- Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol.Frontiers in oncology · 2021Review
- Association BetweenFrontiers in pharmacology · 2021Article
- Immunotherapy in Pediatric B-Cell Acute Lymphoblastic Leukemia: Advances and Ongoing Challenges.Paediatric drugs · 2020Review
- The NSD2 p.E1099K Mutation Is Enriched at Relapse and Confers Drug Resistance in a Cell Context-Dependent Manner in Pediatric Acute Lymphoblastic Leukemia.Molecular cancer research : MCR · 2020Article
- Reversal of glucocorticoid resistance in paediatric acute lymphoblastic leukaemia is dependent on restoring BIM expression.British journal of cancer · 2020Article
- Integrative genomic analyses reveal mechanisms of glucocorticoid resistance in acute lymphoblastic leukemia.Nature cancer · 2020Article
- Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank.The Journal of allergy and clinical immunology · 2020Article
- Relapse-associated AURKB blunts the glucocorticoid sensitivity of B cell acute lymphoblastic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Although great advances have been made in the treatment of pediatric acute lymphoblastic leukemia, up to one of five patients will relapse, and their prognosis thereafter is dismal. We have previously identified recurrent deletions in TBL1XR1, which encodes for an F-box like protein responsible for regulating the nuclear hormone repressor complex stability. Here we model TBL1XR1 deletions in B-precursor ALL cell lines and show that TBL1XR1 knockdown results in reduced glucocorticoid receptor recruitment to glucocorticoid responsive genes and ultimately decreased glucocorticoid signaling caused by increased levels of nuclear hormone repressor 1 and HDAC3. Reduction in glucocorticoid signaling in TBL1XR1-depleted lines resulted in resistance to glucocorticoid agonists, but not to other chemotherapeutic agents. Importantly, we show that treatment with the HDAC inhibitor SAHA restores sensitivity to prednisolone in TBL1XR1-depleted cells. Altogether, our data indicate that loss of TBL1XR1 is a novel driver of glucocorticoid resistance in ALL and that epigenetic therapy may have future application in restoring drug sensitivity at relapse.
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.