ArticleThe Journal of clinical investigation2021
Hyperglycemia cooperates with Tet2 heterozygosity to induce leukemia driven by proinflammatory cytokine-induced lncRNA Morrbid.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Metabolic control of innate immune activation in TET2-mutant clonal hematopoiesis.Cell chemical biology · 2026Article
- The Link between Modifiable Risk Factors and Myeloid Disorders-From Plate to Pathogenesis.Blood cancer discovery · 2026Review
- Disruption of Morrbid alleviates autoinflammatory osteomyelitis in Pstpip2-deficient mice.Disease models & mechanisms · 2025Article
- The Emerging Role of LncRNA AWPPH in Multiple Cancers: A Review Study.Current molecular medicine · 2025Review
- Metabolic reprogramming and epigenetic effects due to reducing sugars and glycation products in cancer.Frontiers in epigenetics and epigenomics · 2025Review
- CHIP: a clonal odyssey of the bone marrow niche.The Journal of clinical investigation · 2024Review
- Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets.Signal transduction and targeted therapy · 2024Review
- Er:YAG Laser Alleviates Inflammaging in Diabetes-Associated Periodontitis via Activation CTBP1-AS2/miR-155/SIRT1 Axis.International journal of molecular sciences · 2024Article
- Blockade of IL-6 signaling alleviates atherosclerosis inNature cardiovascular research · 2023Article
- Obesity-induced inflammation exacerbates clonal hematopoiesis.The Journal of clinical investigation · 2023Article
- Inflammatory signals from fatty bone marrow support DNMT3A driven clonal hematopoiesis.Nature communications · 2023Article
- Myeloid-derived growth factor regulates high glucose-mediated apoptosis of gingival fibroblasts and induce AKT pathway activation and nuclear factor κB pathway inhibition.Journal of dental sciences · 2023Article
- Causes of Clonal Hematopoiesis: a Review.Current oncology reports · 2023Review
- Epigenetic Modification of Cytosines in Hematopoietic Differentiation and Malignant Transformation.International journal of molecular sciences · 2023Review
- Cigarette smoke stimulates clonal expansion of Jak2Frontiers in oncology · 2023Article
- Physioxia-induced downregulation of Tet2 in hematopoietic stem cells contributes to enhanced self-renewal.Blood · 2022Article
- Long Noncoding RNA MIR4435-2HG Suppresses Colorectal Cancer Initiation and Progression By Reprogramming Neutrophils.Cancer immunology research · 2022Article
- Hematopoiesis of Indeterminate Potential and Atherothrombotic Risk.Thrombosis and haemostasis · 2022Review
- Prioritizing risk genes as novel stratification biomarkers for acute monocytic leukemia by integrative analysis.Discover oncology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Diabetes mellitus (DM) is a risk factor for cancer. The role of DM-induced hyperglycemic (HG) stress in blood cancer is poorly understood. Epidemiologic studies show that individuals with DM are more likely to have a higher rate of mutations in genes found in pre-leukemic hematopoietic stem and progenitor cells (pre-LHSPCs) including TET2. TET2-mutant pre-LHSPCs require additional hits to evolve into full-blown leukemia and/or an aggressive myeloproliferative neoplasm (MPN). Intrinsic mutations have been shown to cooperate with Tet2 to promote leukemic transformation. However, the extrinsic factors are poorly understood. Using a mouse model carrying Tet2 haploinsufficiency to mimic the human pre-LHSPC condition and HG stress, in the form of an Ins2Akita/+ mutation, which induces hyperglycemia and type 1 DM, we show that the compound mutant mice developed a lethal form of MPN and/or acute myeloid leukemia (AML). RNA-Seq revealed that this was due in part to upregulation of proinflammatory pathways, thereby generating a feed-forward loop, including expression of the antiapoptotic, long noncoding RNA (lncRNA) Morrbid. Loss of Morrbid in the compound mutants rescued the lethality and mitigated MPN/AML. We describe a mouse model for age-dependent MPN/AML and suggest that hyperglycemia acts as an environmental driver for myeloid neoplasms, which could be prevented by reducing expression levels of the inflammation-related lncRNA Morrbid.
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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.