Download - The Importance of PDGFRB in Leukemia
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The Importance of PDGFRB in Leukemia
Jenny PhungMarch 22, 2005
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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.
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Different PDGFR and Ligands
Hoch & Soriano (2003) Development 130:4771
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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.
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Different Interactions between PDGFRs and Ligands
Hoch & Soriano (2003) Development 130:4772
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PDGFRB’s Functions in Cellular Level Receptor tyrosine kinase.
Ligand binding-> dimerization-> autophosphorylation.
Activates the Ras-MAPK, PI3K, & phospholipase C gamma pathways.
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PDGFR Activation Pathways
Hoch & Soriano (2003) Development 130:4772
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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.
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PDGFB and PDGFRB’s Roles in Angiogenesis
Hoch & Soriano (2003) Development 130:4773
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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.
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ETV6-PDGFRB Fusion Gene
Apperley, et al. (2002) New England J of Medicine 347:483
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Treatment for Activated Tyrosine KinasesPatient 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
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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.