ArticleProceedings of the National Academy of Sciences of the United States of America2010
Mutant Ikzf1, KrasG12D, and Notch1 cooperate in T lineage leukemogenesis and modulate responses to targeted agents.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Single-cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.Blood advances · 2025Article
- Leukemogenic Kras mutation reprograms multipotent progenitors to facilitate its spread through the hematopoietic system.The Journal of experimental medicine · 2025Article
- Opposing effects of KDM6A and JDP2 on glucocorticoid sensitivity in T-ALL.Blood advances · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- Progress in research on childhood T-cell acute lymphocytic leukemia, Notch1 signaling pathway, and its inhibitors: A review.Bosnian journal of basic medical sciences · 2021Review
- Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action.PloS one · 2021Article
- Loss of glucocorticoid receptor expression mediates in vivo dexamethasone resistance in T-cell acute lymphoblastic leukemia.Leukemia · 2020Article
- Convergent genetic aberrations in murine and human T lineage acute lymphoblastic leukemias.PLoS genetics · 2019Article
- High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions.Cell reports · 2019Article
- Mechanistic and Preclinical Insights from Mouse Models of Hematologic Cancer Characterized by Hyperactive Ras.Cold Spring Harbor perspectives in medicine · 2018Review
- Leukemia-specific delivery of mutant NOTCH1 targeted therapy.The Journal of experimental medicine · 2018Article
- Article
- The Capicua tumor suppressor: a gatekeeper of Ras signaling in development and cancer.Cell cycle (Georgetown, Tex.) · 2018Review
- Inactivation of Capicua in adult mice causes T-cell lymphoblastic lymphoma.Genes & development · 2017Article
- Genomic characterization of paediatric acute lymphoblastic leukaemia: an opportunity for precision medicine therapeutics.British journal of haematology · 2017Review
- Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.Haematologica · 2017Article
- Article
- TRIB2 regulates normal and stress-induced thymocyte proliferation.Cell discovery · 2016Article
- Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes.Nature genetics · 2015Article
- Cutting Edge: Codeletion of the Ras GTPase-Activating Proteins (RasGAPs) Neurofibromin 1 and p120 RasGAP in T Cells Results in the Development of T Cell Acute Lymphoblastic Leukemia.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
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12 authors.
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Abstract
Mice that accurately model the genetic diversity found in human cancer are valuable tools for interrogating disease mechanisms and investigating novel therapeutic strategies. We performed insertional mutagenesis with the MOL4070LTR retrovirus in Mx1-Cre, Kras(G12D) mice and generated a large cohort of T lineage acute lymphoblastic leukemias (T-ALLs). Molecular analysis infers that retroviral integration within Ikzf1 is an early event in leukemogenesis that precedes Kras(G12D) expression and later acquisition of somatic Notch1 mutations. Importantly, biochemical analysis uncovered unexpected heterogeneity, which suggests that Ras signaling networks are remodeled during multistep tumorigenesis. We tested tumor-derived cell lines to identify biomarkers of therapeutic response to targeted inhibitors. Whereas all T-ALLs tested were sensitive to a dual-specificity phosphoinosityl 3-kinase/mammalian target of rapamycin inhibitor, biochemical evidence of Notch1 activation correlated with sensitivity to gamma-secretase inhibition. In addition, Kras(G12D) T-ALLs were more responsive to a MAP/ERK kinase inhibitor in vitro and in vivo. Together, these studies identify a genetic pathway involving Ikzf1, Kras(G12D), and Notch1 in T lineage leukemogenesis, reveal unexpected diversity in Ras-regulated signaling networks, and define biomarkers of drug responses that may inform treatment strategies.
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