ArticleLeukemia2012
Aberrant expression of RasGRP1 cooperates with gain-of-function NOTCH1 mutations in T-cell leukemogenesis.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.Cell cycle (Georgetown, Tex.) · 2024Review
- A Focused Review of Ras Guanine Nucleotide-Releasing Protein 1 in Immune Cells and Cancer.International journal of molecular sciences · 2023Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Article
- Identification of leukemia stem cell expression signatures through Monte Carlo feature selection strategy and support vector machine.Cancer gene therapy · 2020Article
- mTOR and other effector kinase signals that impact T cell function and activity.Immunological reviews · 2019Review
- A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis.Cell reports · 2018Article
- Article
- Distinct oncogenic Ras signals characterized by profound differences in flux through the RasGDP/RasGTP cycle.Small GTPases · 2017Article
- The role of wild type RAS isoforms in cancer.Seminars in cell & developmental biology · 2016Review
- MEK and PI3K-AKT inhibitors synergistically block activated IL7 receptor signaling in T-cell acute lymphoblastic leukemia.Leukemia · 2016Article
- Article
- Dysregulated choline metabolism in T-cell lymphoma: role of choline kinase-α and therapeutic targeting.Blood cancer journal · 2015Article
- A novel cell-cycle-indicator, mVenus-p27K-, identifies quiescent cells and visualizes G0-G1 transition.Scientific reports · 2014Article
- Functional redundancy of Sos1 and Sos2 for lymphopoiesis and organismal homeostasis and survival.Molecular and cellular biology · 2013Article
- Gene expression profiling of murine T-cell lymphoblastic lymphoma identifies deregulation of S-phase initiating genes.Leukemia research · 2013Article
- RasGRP Ras guanine nucleotide exchange factors in cancer.Frontiers in biology · 2013Article
- Regulation of ras exchange factors and cellular localization of ras activation by lipid messengers in T cells.Frontiers in immunology · 2013Review
- Article
- Dysregulated RasGRP1 responds to cytokine receptor input in T cell leukemogenesis.Science signaling · 2013Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ras guanyl nucleotide-releasing proteins (RasGRPs) are activators of Ras. Previous studies have indicated the possible involvement of RasGRP1 and RasGRP4 in leukemogenesis. Here, the predominant role of RasGRP1 in T-cell leukemogenesis is clarified. Notably, increased expression of RasGRP1, but not RasGRP4, was frequently observed in human T-cell malignancies. In a mouse bone marrow transplantation model, RasGRP1 exclusively induced T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) after a shorter latency when compared with RasGRP4. Accordingly, Ba/F3 cells transduced with RasGRP1 survived longer under growth factor withdrawal or phorbol ester stimulation than those transduced with RasGRP4, presumably due to the efficient activation of Ras. Intriguingly, NOTCH1 mutations resulting in a gain of function were found in 77% of the RasGRP1-mediated mouse T-ALL samples. In addition, gain-of-function NOTCH1 mutation was found in human T-cell malignancy with elevated expression of RasGRP1. Importantly, RasGRP1 and NOTCH1 signaling cooperated in the progression of T-ALL in the murine model. The leukemogenic advantage of RasGRP1 over RasGRP4 was attenuated by the disruption of a protein kinase C phosphorylation site (RasGRP1(Thr184)) not present on RasGRP4. In conclusion, cooperation between aberrant expression of RasGRP1, a strong activator of Ras, and secondary gain-of-function mutations of NOTCH1 have an important role in T-cell leukemogenesis.
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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.