ArticleLeukemia2012
Connectivity mapping identifies HDAC inhibitors for the treatment of t(4;11)-positive infant acute lymphoblastic leukemia.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05075681 (Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen for Patients With Acute T Cell Lymphoblast Leukemia/ Lymphoblastic Lymphoma Underwenting Haploidenticl Peripheral Blood Stem Cell Transplantation), which is not on this map. Cited by 41 papers.
What it found
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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.
Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen for Patients With Acute T Cell Lymphoblast Leukemia/ Lymphoblastic Lymphoma Underwenting Haploidenticl Peripheral Blood Stem Cell Transplantation
Who cites it
41 citing papers in PubMed, 81 citations in OpenAlex.
- Trial
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- Histone Deacetylase Inhibitors orchestrate epigenetic signalling and alter the nucleoporins and nuclear envelope in cervical cancer.Translational oncology · 2025Article
- Age-Driven Genetic and Epigenetic Heterogeneity in B-ALL.International journal of molecular sciences · 2025Review
- Article
- Selective inhibition of HDAC class IIA as therapeutic intervention for KMT2A-rearranged acute lymphoblastic leukemia.Communications biology · 2024Article
- A complex interplay of intra- and extracellular factors regulates the outcome of fetal- and adult-derived MLL-rearranged leukemia.Leukemia · 2024Article
- CRISPR-Cas9 Library Screening Identifies Novel Molecular Vulnerabilities inInternational journal of molecular sciences · 2023Article
- Using Transcriptomics and Cell Morphology Data in Drug Discovery: The Long Road to Practice.ACS medicinal chemistry letters · 2023Review
- Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia.Nature communications · 2023Article
- Chemo-free maintenance therapy in adult T-cell acute lymphoblastic leukemia: A case report and literature review.Frontiers in pharmacology · 2023Article
- Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.Biomolecules · 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
- Targeted Sequencing of Plasma-Derived vs. Urinary cfDNA from Patients with Triple-Negative Breast Cancer.Cancers · 2022Article
- High-Throughput Drug Library Screening in PrimaryBiomedicines · 2022Article
- Irinotecan Induces Disease Remission in Xenograft Mouse Models of PediatricBiomedicines · 2021Article
- MLL-Rearranged Acute Lymphoblastic Leukemia.Current hematologic malignancy reports · 2020Review
- Review
- Considerations for Strategic Use of High-Throughput Transcriptomics Chemical Screening Data in Regulatory Decisions.Current opinion in toxicology · 2019Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MLL-rearranged infant acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia characterized by a unique gene-expression profile. We uncovered that the activation of particular (proto-onco)genes is mediated by promoter hypomethylation. In search for therapeutic agents capable of targeting these potential cancer-promoting genes, we applied connectivity mapping on a gene expression signature based on the genes most significantly hypomethylated in t(4;11)-positive infant ALL as compared with healthy bone marrows. This analysis revealed histone deacetylase (HDAC) inhibitors as suitable candidates to reverse the unfavorable gene signature. We show that HDAC inhibitors effectively induce leukemic cell death in t(4;11)-positive primary infant ALL cells, accompanied by downregulation of MYC, SET, RUNX1, RAN as well as the MLL-AF4 fusion product. Furthermore, DNA methylation was restored after HDAC inhibitor exposure. Our data underlines the essential role for epigenetic de-regulation in MLL-rearranged ALL. Furthermore, we show, for the first time, that connectivity mapping can indirectly be applied on DNA methylation patterns, providing a rationale for HDAC inhibition in t(4;11)-positive leukemias. Given the presented potential of HDAC inhibitors to target important proto-oncogenes including the leukemia-specific MLL fusion in vitro, these agents should urgently be tested in in vivo models and subsequent clinical trials.
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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.