ArticleScience translational medicine2011
A MEK inhibitor abrogates myeloproliferative disease in Kras mutant mice.
Article in Science translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches.Frontiers in oncology · 2021Pooled it
- Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children's Oncology Group.Cancer discovery · 2024Trial
- Clinical, pharmacokinetic and pharmacodynamic data for the MEK1/2 inhibitor pimasertib in patients with advanced hematologic malignancies.Blood cancer journal · 2015Trial
- Trial
- MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors.The Journal of clinical investigation · 2013Trial
- ELK1 promotes the progress of myeloid leukemia by hindering the differentiation of neutrophils.Experimental hematology & oncology · 2026Article
- Computational insights into synergistic mechanisms of PD-901 and 5-azacitidine targeting PTPN11 (SHP2) E76K mutation in juvenile myelomonocytic leukemia.Frontiers in bioinformatics · 2026Article
- Research progress on the mechanisms of CSF3R mutations in leukemogenesis and treatment strategies.Cancer cell international · 2025Review
- Potential clinical use of azacitidine and MEK inhibitor combination therapy in PTPN11-mutated juvenile myelomonocytic leukemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.Neuro-oncology · 2022Review
- Review
- Review
- Pediatric Neoplasms Presenting with Monocytosis.Current hematologic malignancy reports · 2021Review
- Targeting RAS in pediatric cancer: is it becoming a reality?Current opinion in pediatrics · 2020Review
- KRasExperimental hematology · 2019Article
- Rigosertib ameliorates the effects of oncogenic KRAS signaling in a murine model of myeloproliferative neoplasia.Oncotarget · 2019Article
- Targeting compensatory MEK/ERK activation increases JAK inhibitor efficacy in myeloproliferative neoplasms.The Journal of clinical investigation · 2019Article
- NOX2 inhibition reduces oxidative stress and prolongs survival in murine KRAS-induced myeloproliferative disease.Oncogene · 2019Article
- Article
- [Advances in the treatment of juvenile myelomonocytic leukemia].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Review
6 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
7 authors at 1 institution in 1 country.
Funding
Abstract
Chronic and juvenile myelomonocytic leukemias (CMML and JMML) are aggressive myeloproliferative neoplasms that are incurable with conventional chemotherapy. Mutations that deregulate Ras signaling play a central pathogenic role in both disorders, and Mx1-Cre, Kras(LSL-G12D) mice that express the Kras oncogene develop a fatal disease that closely mimics these two leukemias in humans. Activated Ras controls multiple downstream effectors, but the specific pathways that mediate the leukemogenic effects of hyperactive Ras are unknown. We used PD0325901, a highly selective pharmacological inhibitor of mitogen-activated or extracellular signal-regulated protein kinase kinase (MEK), a downstream component of the Ras signaling network, to address how deregulated Raf/MEK/ERK (extracellular signal-regulated kinase) signaling drives neoplasia in Mx1-Cre, Kras(LSL-G12D) mice. PD0325901 treatment induced a rapid and sustained reduction in leukocyte counts, enhanced erythropoiesis, prolonged mouse survival, and corrected the aberrant proliferation and differentiation of bone marrow progenitor cells. These responses were due to direct effects of PD0325901 on Kras mutant cells rather than to stimulation of normal hematopoietic cell proliferation. Consistent with the in vivo response, inhibition of MEK reversed the cytokine hypersensitivity characteristic of Kras(G12D) hematopoietic progenitor cells in vitro. Our data demonstrate that deregulated Raf/MEK/ERK signaling is integral to the growth of Kras-mediated myeloproliferative neoplasms and further suggest that MEK inhibition could be a useful way to ameliorate functional hematologic abnormalities in patients with CMML and JMML.
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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.