1 / 13

The Importance of PDGFRB in Leukemia

The Importance of PDGFRB in Leukemia. Jenny Phung March 22, 2005. Background Information. What is PDGF? It is also known as platelet-derived growth factor. There are four types of ligands: PDGFA, B, C, and D. PDGF ligands are homodimers. Different PDGFR and Ligands.

dorian-graves
Download Presentation

The Importance of PDGFRB in Leukemia

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. The Importance of PDGFRB in Leukemia Jenny Phung March 22, 2005

  2. Background Information What is PDGF? • It is also known as platelet-derived growth factor. • There are four types of ligands: PDGFA, B, C, and D. • PDGF ligands are homodimers.

  3. Different PDGFR and Ligands Hoch & Soriano (2003) Development 130:4771

  4. If there are PDGF, there must be PDGFRs • Three types of receptors: PDGFR alpha alpha, alpha beta, and beta beta. • The PDGFRBs bind the BB and DD ligands.

  5. Different Interactions between PDGFRs and Ligands Hoch & Soriano (2003) Development 130:4772

  6. PDGFRB’s Functions in Cellular Level • Receptor tyrosine kinase. • Ligand binding-> dimerization-> autophosphorylation. • Activates the Ras-MAPK, PI3K, & phospholipase C gamma pathways.

  7. PDGFR Activation Pathways Hoch & Soriano (2003) Development 130:4772

  8. What does PDGFRB do for the organism? • PDGFRB + PDGFB regulate development of vascular smooth muscle cells and pericytes. • Mice lacking PDGFB or PDGFRB die perinatally with extensive hemorrhaging.

  9. PDGFB and PDGFRB’s Roles in Angiogenesis Hoch & Soriano (2003) Development 130:4773

  10. How is PDGFRB Responsible for Causing Leukemia? • PDGFRB gene on chromosome 5 location 33 is fused with ETV6 gene on chromosome 12 location 13. • Result: Upregulation of PDGFRB in lymphoid cells.

  11. ETV6-PDGFRB Fusion Gene Apperley, et al. (2002) New England J of Medicine 347:483

  12. Treatment for Activated Tyrosine Kinases Patient has a case of chronic myeloproliferative disease with ulcerated skin lesions. Panel A: Before Imatinib treatment Panel B: After 8 months of Imatinib treatment Apperley, et al. (2002) New England J of Medicine 347:481

  13. References • Apperley, JF, Gardembas, M, Melo, JV, et al. Responses to imatinib myselate in patients with chronic myeloproliferative diseases with rearragements of the platelet-derived growt factor receptor beta. New England Journal of Medicine. 2002; 347:481-487. • Cross, NCP and Reiter, A. Tyrosine kinase fusion genes in chronic myeloproliferative diseases. Leukemia. 2002; 16:1207-1212. • Hoch, RV and Soriano, P. Roles of PDGF in animal development. Development. 2003; 130:4769-4784.

More Related