ArticleLeukemia2013
Impairing MLL-fusion gene-mediated transformation by dissecting critical interactions with the lens epithelium-derived growth factor (LEDGF/p75).
Article in Leukemia, 2013. 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, 50 citations in OpenAlex.
- Relationship between the distribution of LEDGF along genes and positions of HIV-1 DNA integration.mBio · 2026Article
- HOXA9 Regulome and Pharmacological Interventions in Leukemia.Advances in experimental medicine and biology · 2024Review
- Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression.European journal of medical genetics · 2023Review
- Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens.Nature communications · 2023Article
- Multivalency of nucleosome recognition by LEDGF.Nucleic acids research · 2023Article
- The TFIIS N-terminal domain (TND): a transcription assembly module at the interface of order and disorder.Biochemical Society transactions · 2023Review
- LEDGF/p75-mediated chemoresistance of mixed-lineage leukemia involves cell survival pathways and super enhancer activators.Cancer gene therapy · 2022Review
- Structure, function and inhibition of critical protein-protein interactions involving mixed lineage leukemia 1 and its fusion oncoproteins.Journal of hematology & oncology · 2021Review
- Article
- Drosophila P75 safeguards oogenesis by preventing H3K9me2 spreading.Journal of genetics and genomics = Yi chuan xue bao · 2020Article
- Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions.Auto- immunity highlights · 2020Review
- Direct and Indirect Targeting of HOXA9 Transcription Factor in Acute Myeloid Leukemia.Cancers · 2019Review
- Polymorphism rs2395655 affects LEDGF/p75 binding activity and p21WAF1/CIP1 gene expression in esophageal squamous cell carcinoma.Cancer medicine · 2019Article
- Therapeutic targeting potential of chromatin-associated proteins in MLL-rearranged acute leukemia.Cellular oncology (Dordrecht, Netherlands) · 2019Review
- Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- CARM1 Is Essential for Myeloid Leukemogenesis but Dispensable for Normal Hematopoiesis.Cancer cell · 2018Article
- LEDGF/p75 is dispensable for hematopoiesis but essential for MLL-rearranged leukemogenesis.Blood · 2018Article
- Article
- Targeting the stress oncoprotein LEDGF/p75 to sensitize chemoresistant prostate cancer cells to taxanes.Oncotarget · 2017Article
- The molecular mechanics of mixed lineage leukemia.Oncogene · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lens epithelium-derived growth factor (LEDGF/p75) tethers the mixed-lineage leukemia (MLL1) protein complex to chromatin. Likewise, LEDGF/p75 tethers the HIV-1 pre-integration complex to chromatin. We previously demonstrated that expression of the C-terminal fragment fused to enhanced green fluorescent protein (eGFP) (eGFP-LEDGF(325-530)) impaired HIV-1 replication. Here, we explored this strategy to selectively interfere with the leukemogenic activity of MLL-fusion proteins. We found that expression of LEDGF(325-530) impaired the clonogenic growth of MLL-fusion gene transformed human and mouse hematopoietic cells, without affecting the growth of control cells immortalized by the FLT3-ITD mutant or normal lineage-marker-depleted murine bone marrow cells. Expression of LEDGF(325-530) was associated with downregulation of the MLL target Hoxa9 and impaired cell cycle progression. Structure-function analysis revealed two small eGFP-fused LEDGF/p75 peptides, LEDGF(424-435) and LEDGF(375-386) phenocopying these effects. Both LEDGF(325-530) and the smaller active peptides were able to disrupt the LEDGF/p75-MLL interaction. Expression of LEDGF(325-530) or LEDGF(375-386) fragments increased the latency period to disease development in vivo in a mouse bone marrow transplant model of MLL-AF9-induced AML. We conclude that small peptides disrupting the LEDGF/p75-MLL interface have selective anti-leukemic activity providing a direct rationale for the design of small molecule inhibitors targeting this interaction.
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.