ArticleThe Journal of clinical investigation2017
Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 70 citations in OpenAlex.
- Targeting DOT1L Reactivates HERV-K to Drive Cell-Autonomous and Paracrine Senescence in Adenocarcinoma of the Esophagogastric Junction.Cancer research · 2026Article
- Mechanism of AF9 (MLLT3)-Partner Dissociation in Mixed-Lineage Leukemia-Rearranged Leukemia.JACS Au · 2026Article
- Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.International journal of cancer · 2026Review
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells.Communications biology · 2025Article
- Only InfantInternational journal of molecular sciences · 2024Article
- Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression.European journal of medical genetics · 2023Review
- Dot1l cooperates with Npm1 to repress endogenous retrovirus MERVL in embryonic stem cells.Nucleic acids research · 2023Article
- MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins.Nature communications · 2023Article
- The ENL YEATS epigenetic reader domain critically links MLL-ENL to leukemic stem cell frequency in t(11;19) Leukemia.Leukemia · 2023Article
- Role of the MOZ/MLL-mediated transcriptional activation system for self-renewal in normal hematopoiesis and leukemogenesis.The FEBS journal · 2022Review
- MOZ is critical for the development of MOZ/MLL fusion-induced leukemia through regulation of Hoxa9/Meis1 expression.Blood advances · 2022Article
- MiR-27a downregulates 14-3-3θ, RUNX1, AF4, and MLL-AF4, crucial drivers of blast transformation in t(4;11) leukemia cells.Cell biochemistry and function · 2022Article
- Improvements in allogeneic hematopoietic cell transplantation outcomes for adults with ALL over the past 3 decades.Blood advances · 2022Article
- Childhood acute myeloid leukemia with 5q deletion and HNRNPH1-MLLT10 fusion: the first case report.Blood advances · 2022Article
- Targeting matrix metallopeptidase 2 by hydroxyurea selectively kills acute myeloid mixed-lineage leukemia.Cell death discovery · 2022Article
- Targeting the histone H3 lysine 79 methyltransferase DOT1L in MLL-rearranged leukemias.Journal of hematology & oncology · 2022Review
- MLL::AF9 degradation induces rapid changes in transcriptional elongation and subsequent loss of an active chromatin landscape.Molecular cell · 2022Article
- Multifaceted roles of YEATS domain-containing proteins and novel links to neurological diseases.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The eleven-nineteen leukemia (ENL) protein family, composed of ENL and AF9, is a common component of 3 transcriptional modulators: AF4-ENL-P-TEFb complex (AEP), DOT1L-AF10-ENL complex (referred to as the DOT1L complex) and polycomb-repressive complex 1 (PRC1). Each complex associates with chromatin via distinct mechanisms, conferring different transcriptional properties including activation, maintenance, and repression. The mixed-lineage leukemia (MLL) gene often fuses with ENL and AF10 family genes in leukemia. However, the functional interrelationship among those 3 complexes in leukemic transformation remains largely elusive. Here, we have shown that MLL-ENL and MLL-AF10 constitutively activate transcription by aberrantly inducing both AEP-dependent transcriptional activation and DOT1L-dependent transcriptional maintenance, mostly in the absence of PRC1, to fully transform hematopoietic progenitors. These results reveal a cooperative transcriptional activation mechanism of AEP and DOT1L and suggest a molecular rationale for the simultaneous inhibition of the MLL fusion-AF4 complex and DOT1L for more effective treatment of MLL-rearranged leukemia.
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.