1 / 12

Notch and T-cell acute Lymphoblastic leukemias

Notch and T-cell acute Lymphoblastic leukemias. by Ana Ruth Cerna March 2 th , 2006. Intro to Notch. Notch proteins: Transmembrane receptors w/ different domains. Ligands include: Jagged and Delta-like Synthesized as precursor to be proteolytically processed Work in:

Download Presentation

Notch and T-cell acute Lymphoblastic leukemias

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Notch and T-cell acute Lymphoblastic leukemias by Ana Ruth Cerna March 2th, 2006

  2. Intro to Notch • Notch proteins: • Transmembrane receptors w/ different domains. • Ligands include: Jagged and Delta-like • Synthesized as precursor to be proteolytically processed • Work in: • Lateral signaling that influence cell-fate decisions. Inductive cell fate decisions. • Proliferation • Apoptosis

  3. Notch Signaling

  4. Role of Notch in T-cell development • Part of T-cell development at various stages: • T/B cell fate determination by Notch1 signaling • / and / lineage decision • And CD4/CD8 lineage commitment

  5. T-Cell Development http://www.med.upenn.edu/immun/images/PearGRAPHIC.gif

  6. T-Cell Development http://www.niaid.nih.gov/dir/labs/LCMI/development.gif

  7. T-Cell Acute Lymphoblastic Leukemia (T-ALL) & Notch • Constant Notch activation caused by point mutations, translocations and other mechanisms. • Over expression of Notch: • Enhances thymocyte survival and proliferation. • Increased number of immature T Cell progenitors. Increases likelihood of other mutations that could affect development.

  8. Mice models—inactivation of Notch1 Immunity, Vol. 10, 547-558, May, 1999

  9. Inactivation of Notch1 leads to retarded growth Immunity, Vol. 10, 547-558, May, 1999

  10. Constitutive Activation of Notch and relationship to T-ALL Mol Cell Biol. 2004 November; 24(21): 9265–9273. doi: 10.1128/MCB.24.21.9265-9273.2004 Constitutive activation of Notch in mice as well as in T-ALL results in the overpopulation of immature t-cells in different tissues, which can be seen dramatically as an oversized spleen and mesenteric lymph node in the picture above.

  11. In Summary • Notch influences cancer development by affecting cell fate, proliferation, and apoptosis. • Mouse models provide a great way to study Notch signaling pathway. Interesting to point out that Notch is also involved in other human cancers such as: pancreatic cancer, medulloblastoma Y mucoepidermoid carcinoma.

  12. RESH_Story_Notch_Full by Thomas Schmitt.jpg

More Related