ArticleBlood2009
Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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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.
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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.
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Who cites it
63 citing papers in PubMed, 98 citations in OpenAlex.
- Mll5 haploinsufficiency attenuates microglial phagocytosis through dysregulated TREM2-SGK3-GSK3β signaling and recapitulates ASD-like behaviors in mice.Nature communications · 2026Article
- Shaping neutrophil morphology and function: the importance of a segmented nucleus.Nature reviews. Immunology · 2026Review
- Multiplex gene editing models of del(7q) reveal combinedBlood neoplasia · 2025Article
- Differential H4K16ac levels ensure a balance between quiescence and activation in hematopoietic stem cells.Science advances · 2021Article
- Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549.Oncology letters · 2021Article
- MLL5 improves ATRA driven differentiation and promotes xenotransplant engraftment in acute promyelocytic leukemia model.Cell death & disease · 2021Article
- Case Report:Frontiers in pediatrics · 2021Article
- A chromatin perspective on metabolic and genotoxic impacts on hematopoietic stem and progenitor cells.Cellular and molecular life sciences : CMLS · 2020Review
- The core spliceosomal factor U2AF1 controls cell-fate determination via the modulation of transcriptional networks.RNA biology · 2020Article
- Genomic Signatures of Selection Associated With Litter Size Trait in Jining Gray Goat.Frontiers in genetics · 2020Article
- Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.American journal of human genetics · 2019Article
- SET domains and stress: uncovering new functions for yeast Set4.Current genetics · 2019Review
- Set3 Is Required for Asexual Development, Aflatoxin Biosynthesis, and Fungal Virulence inFrontiers in microbiology · 2019Article
- Epigenetics in myelodysplastic syndromes.Seminars in cancer biology · 2018Review
- SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity.eLife · 2018Article
- MLL5 suppresses antiviral innate immune response by facilitating STUB1-mediated RIG-I degradation.Nature communications · 2018Article
- Therapy-related myeloid neoplasms: when genetics and environment collide.Nature reviews. Cancer · 2017Review
- Cytogenetic Abnormalities in Myelodysplastic Syndromes: An Overview.International journal of hematology-oncology and stem cell research · 2017Review
- MLL5 (KMT2E): structure, function, and clinical relevance.Cellular and molecular life sciences : CMLS · 2017Review
- The BAF45a/PHF10 subunit of SWI/SNF-like chromatin remodeling complexes is essential for hematopoietic stem cell maintenance.Experimental hematology · 2017Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MLL5 is a divergent member of the Drosophila Trithorax-related (SET) domain and plant homeodomain (PHD) domain-containing chromatin regulators that are involved in the regulation of transcriptional "memory" during differentiation. Human MLL5 is located on chromosome 7q22, which frequently is deleted in myeloid leukemias, suggesting a possible role in hemopoiesis. To address this question, we generated a loss-of-function allele (Mll5(tm1Apa)) in the murine Mll5 locus. Unlike other Mll genes, Mll5(tm1Apa) homozygous mice are viable but display defects in immunity and hematopoiesis. First, Mll5(tm1Apa) homozygous mice show increased susceptibility to spontaneous eye infections, associated with a cell-autonomous impairment of neutrophil function. Second, Mll5(tm1Apa/tm1Apa) mice exhibit a mild impairment of erythropoiesis. Third, Mll5(tm1Apa/tm1Apa) hematopoietic stem cells (HSCs) have impaired competitive repopulating capacity both under normal conditions and when subjected to self-renewal stimulation by NUP98-HOXA10. Fourth, Mll5(tm1Apa) homozygous HSCs show a dramatic sensitivity to DNA demethylation-induced differentiation (5-azadeoxycytidine). Taken together, our data show that MLL5 is involved in terminal myeloid differentiation and the regulation of HSC self-renewal by a mechanism that involves DNA methylation. These data warrant investigation of MLL5 expression levels as a predictive marker of demethylating-agent response in patients with myelodysplastic syndromes and leukemias and identify MLL5 as a key regulator of normal hematopoiesis.
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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.