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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.

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The Importance of PDGFRB in Leukemia

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  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.

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