The Importance of PDGFRB in Leukemia
-
Upload
dorian-graves -
Category
Documents
-
view
34 -
download
1
description
Transcript of The Importance of PDGFRB in Leukemia
![Page 1: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/1.jpg)
1
The Importance of PDGFRB in Leukemia
Jenny PhungMarch 22, 2005
![Page 2: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/2.jpg)
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.
![Page 3: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/3.jpg)
3
Different PDGFR and Ligands
Hoch & Soriano (2003) Development 130:4771
![Page 4: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/4.jpg)
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.
![Page 5: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/5.jpg)
5
Different Interactions between PDGFRs and Ligands
Hoch & Soriano (2003) Development 130:4772
![Page 6: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/6.jpg)
6
PDGFRB’s Functions in Cellular Level Receptor tyrosine kinase.
Ligand binding-> dimerization-> autophosphorylation.
Activates the Ras-MAPK, PI3K, & phospholipase C gamma pathways.
![Page 7: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/7.jpg)
7
PDGFR Activation Pathways
Hoch & Soriano (2003) Development 130:4772
![Page 8: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/8.jpg)
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.
![Page 9: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/9.jpg)
9
PDGFB and PDGFRB’s Roles in Angiogenesis
Hoch & Soriano (2003) Development 130:4773
![Page 10: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/10.jpg)
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.
![Page 11: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/11.jpg)
11
ETV6-PDGFRB Fusion Gene
Apperley, et al. (2002) New England J of Medicine 347:483
![Page 12: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/12.jpg)
12
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
![Page 13: The Importance of PDGFRB in Leukemia](https://reader035.fdocuments.us/reader035/viewer/2022062421/56812ad1550346895d8eb0f2/html5/thumbnails/13.jpg)
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.