ArticleThe Journal of clinical investigation2018
Chromatin regulator Asxl1 loss and Nf1 haploinsufficiency cooperate to accelerate myeloid malignancy.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Oncogenic activation of EVC/EVC2 defines a therapeutically targetable subset of acute myeloid leukemia.Leukemia · 2026Article
- Landscape and clinicopathologic features of RAS pathway mutations in chronic myelomonocytic leukemia.Blood advances · 2025Article
- Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells.Nature genetics · 2024Article
- Protein phosphatase 1 regulatory subunit 15 A promotes translation initiation and induces G2M phase arrest during cuproptosis in cancers.Cell death & disease · 2024Article
- Targeting lysine demethylase 6B ameliorates ASXL1 truncation-mediated myeloid malignancies in preclinical models.The Journal of clinical investigation · 2024Article
- Epigenetic regulation by ASXL1 in myeloid malignancies.International journal of hematology · 2023Review
- Role of ASXL1 in hematopoiesis and myeloid diseases.Experimental hematology · 2022Review
- Review
- ASXL1/2 mutations and myeloid malignancies.Journal of hematology & oncology · 2022Review
- Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors.International journal of molecular sciences · 2022Review
- Article
- Integrated Multi-Omics Analysis Identified PTPRG and CHL1 as Key Regulators of Immunophenotypes in Clear Cell Renal Cell Carcinoma(ccRCC).Frontiers in oncology · 2022Article
- Review
- INTS11 regulates hematopoiesis by promoting PRC2 function.Science advances · 2021Article
- Novel Targeted Therapeutics in Acute Myeloid Leukemia: an Embarrassment of Riches.Current hematologic malignancy reports · 2021Review
- Impacts of NF1 Gene Mutations and Genetic Modifiers in Neurofibromatosis Type 1.Frontiers in neurology · 2021Review
- The Functions and Mechanisms of PR-DUB in Malignancy.Frontiers in molecular biosciences · 2021Review
- Deregulation of tumor suppressive ASXL1-PTEN/AKT axis in myeloid malignancies.Journal of molecular cell biology · 2020Article
- The role of ASXL1 in hematopoiesis and myeloid malignancies.Cellular and molecular life sciences : CMLS · 2019Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
ASXL1 is frequently mutated in myeloid malignancies and is known to co-occur with other gene mutations. However, the molecular mechanisms underlying the leukemogenesis associated with ASXL1 and cooperating mutations remain to be elucidated. Here, we report that Asxl1 loss cooperated with haploinsufficiency of Nf1, a negative regulator of the RAS signaling pathway, to accelerate the development of myeloid leukemia in mice. Loss of Asxl1 and Nf1 in hematopoietic stem and progenitor cells resulted in a gain-of-function transcriptional activation of multiple pathways such as MYC, NRAS, and BRD4 that are critical for leukemogenesis. The hyperactive MYC and BRD9 transcription programs were correlated with elevated H3K4 trimethylation at the promoter regions of genes involving these pathways. Furthermore, pharmacological inhibition of both the MAPK pathway and BET bromodomain prevented leukemia initiation and inhibited disease progression in Asxl1Δ/Δ Nf1Δ/Δ mice. Concomitant mutations of ASXL1 and RAS pathway genes were associated with aggressive progression of myeloid malignancies in patients. This study sheds light on the effect of cooperation between epigenetic alterations and signaling pathways on accelerating the progression of myeloid malignancies and provides a rational therapeutic strategy for the treatment of myeloid malignancies with ASXL1 and RAS pathway gene mutations.
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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.