ArticleThe Journal of clinical investigation2013
Normal hematopoiesis and neurofibromin-deficient myeloproliferative disease require Erk.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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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Who cites it
37 citing papers in PubMed, 43 citations in OpenAlex.
- BST2 facilitates activation of hematopoietic stem cells through ERK signaling.Experimental hematology · 2024Article
- Molecular regulation of hematopoietic stem cell quiescence.Cellular and molecular life sciences : CMLS · 2022Review
- RAS and beyond: the many faces of the neurofibromatosis type 1 protein.Disease models & mechanisms · 2022Article
- Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.Frontiers in oncology · 2022Review
- MEK inhibition exerts temporal and myeloid cell-specific effects in the pathogenesis of neurofibromatosis type 1 arteriopathy.Scientific reports · 2021Article
- New Insights into the Pathogenesis of Systemic Mastocytosis.International journal of molecular sciences · 2021Review
- MEKK2 mediates aberrant ERK activation in neurofibromatosis type I.Nature communications · 2020Article
- Article
- ERK Activity in Immature Leukemic Cells Drives Clonal Selection during Induction Therapy for Acute Myeloid Leukemia.Scientific reports · 2020Article
- Cdkn2a (Arf) loss drives NF1-associated atypical neurofibroma and malignant transformation.Human molecular genetics · 2019Article
- MAPK/ERK Signaling in Regulation of Renal Differentiation.International journal of molecular sciences · 2019Review
- Targeting compensatory MEK/ERK activation increases JAK inhibitor efficacy in myeloproliferative neoplasms.The Journal of clinical investigation · 2019Article
- An ERK-Dependent Feedback Mechanism Prevents Hematopoietic Stem Cell Exhaustion.Cell stem cell · 2018Article
- Mechanistic and Preclinical Insights from Mouse Models of Hematologic Cancer Characterized by Hyperactive Ras.Cold Spring Harbor perspectives in medicine · 2018Review
- Inhibition of MEK/ERK signalling pathway promotes erythroid differentiation and reduces HSCs engraftment in ex vivo expanded haematopoietic stem cells.Journal of cellular and molecular medicine · 2018Article
- Saponins fromFrontiers in pharmacology · 2017Article
- MEK1 is required for the development of NRAS-driven leukemia.Oncotarget · 2016Article
- Trametinib Drives T-cell-Dependent Control of KRAS-Mutated Tumors by Inhibiting Pathological Myelopoiesis.Cancer research · 2016Article
- The role of nerve microenvironment for neurofibroma development.Oncotarget · 2016Article
- Effector T cell subclasses associate with tumor burden in neurofibromatosis type 1 patients.Cancer immunology, immunotherapy : CII · 2016Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Neurofibromatosis type 1 (NF1) predisposes individuals to the development of juvenile myelomonocytic leukemia (JMML), a fatal myeloproliferative disease (MPD). In genetically engineered murine models, nullizygosity of Nf1, a tumor suppressor gene that encodes a Ras-GTPase-activating protein, results in hyperactivity of Raf/Mek/Erk in hematopoietic stem and progenitor cells (HSPCs). Activated Erk1/2 phosphorylate kinases and transcription factors with myriad mitogenic roles in diverse cell types. However, genetic studies examining Erk1/2's differential and/or combined control of normal and Nf1-deficient myelopoiesis are lacking. Moreover, prior studies relying on chemical Mek/Erk inhibitors have reached conflicting conclusions in normal and Nf1-deficient mice. Here, we show that while single Erk1 or Erk2 disruption did not grossly compromise myelopoiesis, dual Erk1/2 disruption rapidly ablated granulocyte and monocyte production in vivo, diminished progenitor cell number, and prevented HSPC proliferation in vitro. Genetic disruption of Erk1/2 in the context of Nf1 nullizygosity (Mx1Cre(+)Nf1(flox/flox)Erk1(-/-)Erk2(flox/flox)) fully protects against the development of MPD. Collectively, we identified a fundamental requirement for Erk1/2 signaling in normal and Nf1-deficient hematopoiesis, elucidating a critical hematopoietic function for Erk1/2 while genetically validating highly selective Mek/Erk inhibitors in a leukemia that is otherwise resistant to traditional therapy.
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Registered trials
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