ArticleLeukemia2018
The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity against MLL-rearranged acute lymphoblastic leukaemia and involves the RNF20/RNF40/WAC-H2B ubiquitination axis.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 73 citations in OpenAlex.
- From cell lines to PDXs: in vivo confirmation of synergistic drug responses identified in leukemia cell line models.Blood neoplasia · 2026Article
- E3 ubiquitin ligase RNF40: Structure, function and its context‑dependent roles in tumorigenesis (Review).Oncology reports · 2026Review
- Review
- Decoding RNF20: an epigenetic modifier and beyond.Frontiers in cell and developmental biology · 2026Review
- S-adenosylmethionine addiction confers sensitivity to methionine restriction inHaematologica · 2025Article
- Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradationActa pharmaceutica Sinica. B · 2025Article
- Selective inhibition of HDAC class IIA as therapeutic intervention for KMT2A-rearranged acute lymphoblastic leukemia.Communications biology · 2024Article
- PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer.Journal of translational medicine · 2024Article
- A complex interplay of intra- and extracellular factors regulates the outcome of fetal- and adult-derived MLL-rearranged leukemia.Leukemia · 2024Article
- Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: a systematic review.Frontiers in oncology · 2024Review
- Advancing Diagnostics and Therapy to Reach Universal Cure in Childhood ALL.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Review
- CRISPR-Cas9 Library Screening Identifies Novel Molecular Vulnerabilities inInternational journal of molecular sciences · 2023Article
- Bone Marrow Microenvironment-Induced Chemoprotection inCancers · 2023Article
- Using Transcriptomics and Cell Morphology Data in Drug Discovery: The Long Road to Practice.ACS medicinal chemistry letters · 2023Review
- Updates inBiomedicines · 2023Review
- Updates in infant acute lymphoblastic leukemia and the potential for targeted therapy.Hematology. American Society of Hematology. Education Program · 2022Article
- A Comprehensive Overview of Recent Advances in Epigenetics in Pediatric Acute Lymphoblastic Leukemia.Cancers · 2022Review
- Panobinostat (LBH589) increase survival in adult xenografic model of acute lymphoblastic leukemia with t(4;11) but promotes antagonistic effects in combination with MTX and 6MP.Medical oncology (Northwood, London, England) · 2022Article
- Review
- Genome-wide CRISPR/Cas9 screening identifies determinant of panobinostat sensitivity in acute lymphoblastic leukemia.Blood advances · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
MLL-rearranged acute lymphoblastic leukaemia (ALL) represents an aggressive malignancy in infants (<1 year of age), associated with poor outcome. Current treatment intensification is not further possible, and novel therapy strategies are needed. Notably, MLL-rearranged ALL is characterised by a strongly deregulated epigenome and shows sensitivity to epigenetic perturbators. Here we demonstrate the in vivo efficacy of the histone deacetylase inhibitor panobinostat (LBH589) using xenograft mouse models of MLL-rearranged ALL. Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival and reducing overall disease burden. Comprehensive molecular analyses in vitro showed that this anti-leukaemic activity involves depletion of H2B ubiquitination via suppression of the RNF20/RNF40/WAC E3 ligase complex; a pivotal pathway for MLL-rearranged leukaemic maintenance. Knockdown of WAC phenocopied loss of H2B ubiquitination and concomitant cell death induction. These combined data demonstrate that panobinostat cross-inhibits multiple epigenetic pathways, ultimately contributing to its highly efficacious targeting of MLL-rearranged ALL.
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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.