ArticleLeukemia2016
Targeting the PI3K/Akt pathway in murine MDS/MPN driven by hyperactive Ras.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches.Frontiers in oncology · 2021Pooled it
- [The role of AKT inhibitors combined with Ruxolitinib in ameliorating myeloproliferative disorders in mice with CALR gene mutations].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Research progress on the mechanisms of CSF3R mutations in leukemogenesis and treatment strategies.Cancer cell international · 2025Review
- Aurora Kinase A inhibition enhances DNA damage and tumor cell death withEJNMMI research · 2024Article
- MEK/ERK and PI3K/AKT pathway inhibitors affect the transformation of myelodysplastic syndrome into acute myeloid leukemia via H3K27me3 methylases and de‑methylases.International journal of oncology · 2023Article
- XBP1 promotes NRASJournal of cellular and molecular medicine · 2023Article
- Article
- The genetics of myelodysplastic syndromes and the opportunities for tailored treatments.Frontiers in oncology · 2022Review
- Nf1 and Sh2b3 mutations cooperate in vivo in a mouse model of juvenile myelomonocytic leukemia.Blood advances · 2021Article
- Mutations in chronic myelomonocytic leukemia and their prognostic relevance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- Pediatric Neoplasms Presenting with Monocytosis.Current hematologic malignancy reports · 2021Review
- Proteomic Analysis of an Induced Pluripotent Stem Cell Model Reveals Strategies to Treat Juvenile Myelomonocytic Leukemia.Journal of proteome research · 2020Article
- Tissue-Specific Oncogenic Activity of KRASCancer discovery · 2019Article
- Rigosertib ameliorates the effects of oncogenic KRAS signaling in a murine model of myeloproliferative neoplasia.Oncotarget · 2019Article
- Article
- Germline and SomaticCancer prevention research (Philadelphia, Pa.) · 2018Article
- Wild-type Kras expands and exhausts hematopoietic stem cells.JCI insight · 2018Article
- Mechanistic and Preclinical Insights from Mouse Models of Hematologic Cancer Characterized by Hyperactive Ras.Cold Spring Harbor perspectives in medicine · 2018Review
- Targeting few to help hundreds: JAK, MAPK and ROCK pathways as druggable targets in atypical chronic myeloid leukemia.Molecular cancer · 2018Review
- Survival of pancreatic cancer cells lacking KRAS function.Nature communications · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic and juvenile myelomonocytic leukemias (CMML and JMML) are myelodysplastic/myeloproliferative neoplasia (MDS/MPN) overlap syndromes that respond poorly to conventional treatments. Aberrant Ras activation because of NRAS, KRAS, PTPN11, CBL and NF1 mutations is common in CMML and JMML. However, no mechanism-based treatments currently exist for cancers with any of these mutations. An alternative therapeutic strategy involves targeting Ras-regulated effector pathways that are aberrantly activated in CMML and JMML, which include the Raf/MEK/ERK and phosphoinositide-3'-OH kinase (PI3K)/Akt cascades. Mx1-Cre, Kras(D12) and Mx1-Cre, Nf1(flox/)(-) mice accurately model many aspects of CMML and JMML. Treating Mx1-Cre, Kras(D12) mice with GDC-0941 (also referred to as pictilisib), an orally bioavailable inhibitor of class I PI3K isoforms, reduced leukocytosis, anemia and splenomegaly while extending survival. However, GDC-0941 treatment attenuated activation of both PI3K/Akt and Raf/MEK/ERK pathways in primary hematopoietic cells, suggesting it could be acting through suppression of Raf/MEK/ERK signals. To interrogate the importance of the PI3K/Akt pathway specifically, we treated mice with the allosteric Akt inhibitor MK-2206. This compound had no effect on Raf/MEK/ERK signaling, yet it also induced robust hematologic responses in Kras and Nf1 mice with MPN. These data support investigating PI3K/Akt pathway inhibitors as a therapeutic strategy in JMML and CMML patients.
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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.