ReviewExperimental hematology2015
Targeting DOT1L and HOX gene expression in MLL-rearranged leukemia and beyond.
Review in Experimental hematology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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
77 citing papers in PubMed, 121 citations in OpenAlex.
- Trial
- Beyond nuclear export: chromatin-bound XPO1/CRM1 as a transcriptional scaffold.International journal of hematology · 2026Review
- Review
- Therapeutic Advances in Adult B-cell Acute Lymphoblastic Leukemia with KMT2A Rearrangements.Annals of hematology · 2026Review
- Homocysteine and S-adenosyl-L-homocysteine impair development and methylation in yeast and flies.Disease models & mechanisms · 2026Article
- Review
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- Pediatric leukemia: origins, pathogenesis, the role of microenvironment and immunological modulation.Frontiers in immunology · 2026Review
- Menin inhibitors as targeted therapy in KMT2A-Rearranged acute leukemia: A comprehensive review of current advances and therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- NUP214 in Acute Myeloid Leukemia.Cells · 2025Review
- Review
- T-cell acute lymphoblastic leukaemia: subtype prevalence, clinical outcome, and emerging targeted treatments.Leukemia · 2025Review
- Menin inhibitors for the treatment of acute myeloid leukemia: challenges and opportunities ahead.Journal of hematology & oncology · 2024Review
- Rational design of small-sized peptidomimetic inhibitors disrupting protein-protein interaction.RSC medicinal chemistry · 2024Review
- The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia.Oncogene · 2024Article
- Multiple machine-learning tools identifying prognostic biomarkers for acute Myeloid Leukemia.BMC medical informatics and decision making · 2024Article
- Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment.Journal of experimental & clinical cancer research : CR · 2023Review
- Synthesis of ubiquitinated proteins for biochemical and functional analysis.Chemical science · 2023Review
- Downregulation of DNA methylation enhances differentiation of THP-1 cells and induces M1 polarization of differentiated macrophages.Scientific reports · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Leukemias harboring mixed-lineage leukemia gene (MLL1) abnormalities are associated with poor clinical outcomes, and new therapeutic approaches are desperately needed. Rearrangement of the MLL1 gene generates chimeric proteins that fuse the NH3 terminus of MLL1 to the COOH terminus of its translocation partners. These MLL1 fusion oncoproteins drive the expression of homeobox genes such as HOXA cluster genes and myeloid ecotropic viral integration site 1 homolog (MEIS1), which are known to induce leukemic transformation of hematopoietic progenitors. Genomewide histone methylation studies have revealed that the abnormal expression of MLL1 fusion target genes is associated with high levels of H3K79 methylation at these gene loci. The only known enzyme that catalyzes methylation of H3K79 is disruptor of telomeric-silencing 1-like (DOT1L). Loss-of-function mouse models, as well as small molecular inhibitors of DOT1L, illustrate that leukemias driven by MLL1 translocations are dependent on DOT1L enzymatic activity for proliferation and for the maintenance of HOXA gene expression. Furthermore, DOT1L also appears to be important for HOXA gene expression in other settings including leukemias with select genetic abnormalities. These discoveries have established a foundation for disease-specific therapies that target chromatin modifications in highly malignant leukemias harboring specific genetic abnormalities. This review focuses on the molecular mechanisms underlying MLL1 translocation-driven leukemogenesis and the latest progress on DOT1L-targeted epigenetic therapies for MLL1-rearranged and other leukemias.
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.