ArticleLeukemia2015
Wild-type KRAS inhibits oncogenic KRAS-induced T-ALL in mice.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Progression and perspectives in disease modeling for Juvenile myelomonocytic leukemia.Medical oncology (Northwood, London, England) · 2024Review
- Dose-dependent effects of Dnmt3a in an inducible murine model of KrasExperimental hematology · 2024Article
- Novel Insights into the Role of Kras in Myeloid Differentiation: Engaging with Wnt/β-Catenin Signaling.Cells · 2023Review
- Loss of the wild-type KRAS allele promotes pancreatic cancer progression through functional activation of YAP1.Oncogene · 2021Article
- Role of PLEXIND1/TGFβ Signaling Axis in Pancreatic Ductal Adenocarcinoma Progression Correlates with the Mutational Status ofCancers · 2021Article
- Ras isoform-specific expression, chromatin accessibility, and signaling.Biophysical reviews · 2021Review
- Oncogenic cooperation between TCF7-SPI1 and NRAS(G12D) requires β-catenin activity to drive T-cell acute lymphoblastic leukemia.Nature communications · 2021Article
- Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Silencing of Oncogenic KRAS by Mutant-Selective Small Interfering RNA.ACS pharmacology & translational science · 2021Article
- Knockout of the RAS endoprotease RCE1 accelerates myeloid leukemia by downregulating GADD45b.Leukemia · 2021Article
- Small molecule inhibitors of RAS proteins with oncogenic mutations.Cancer metastasis reviews · 2020Review
- The Mystery of Rap1 Suppression of Oncogenic Ras.Trends in cancer · 2020Review
- KRasExperimental hematology · 2019Article
- Kras promotes myeloid differentiation through Wnt/β-catenin signaling.FASEB bioAdvances · 2019Article
- Article
- Mice expressing KrasG12D in hematopoietic multipotent progenitor cells develop neonatal myeloid leukemia.The Journal of clinical investigation · 2017Article
- Mutant allele specific imbalance in oncogenes with copy number alterations: Occurrence, mechanisms, and potential clinical implications.Cancer letters · 2017Review
- Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design.Nature reviews. Drug discovery · 2016Review
- The role of wild type RAS isoforms in cancer.Seminars in cell & developmental biology · 2016Review
- Loss of wild-type Kras promotes activation of all Ras isoforms in oncogenic Kras-induced leukemogenesis.Leukemia · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of hyperactive RAS signaling is well established in myeloid malignancies but less clear in T-cell malignancies. The Kras2(LSL)Mx1-Cre (KM) mouse model expresses endogenous KRAS(G12D) in hematopoietic cells and is widely used to study mechanisms and treatment of myeloproliferative neoplasms (MPN). The model displays an intriguing shift from MPN to acute T-cell leukemia (T-ALL) after transplantation to wild-type mice, but the mechanisms underlying this lineage shift is unknown. Here, we show that KRAS(G12D) increases proliferation of both myeloid and T-cell progenitors, but whereas myeloid cells differentiate, T-cell differentiation is inhibited at early stages. Secondary mutations in the expanded pool of T-cell progenitors accompany T-ALL development, and our results indicate that the shift from myeloid to T-lymphoid malignancy after transplantation is explained by the increased likelihood for secondary mutations when the tumor lifespan is increased. We demonstrate that tumor lifespan increases after transplantation because primary KM mice die rapidly, not from MPN, but from KRAS(G12D) expression in nonhematopoietic cells, which causes intestinal bleeding and severe anemia. We also identify loss of the wild-type KRAS allele as a secondary mutation in all T-ALL cells and provide evidence that wild-type KRAS acts as a tumor suppressor in the T-cell lineage in mice.
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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.