Gleevecs mechanism of Action

The animation begins by introducing the Philadelphia Chromosome, the result of a reciprocal translocation between chromosomes 9 and 22. More specifically the breakpoint cluster region (BCR) of chromosome 22 is fused with part of the Abelson (ABL) gene on chromosome 9. The resulting BCR-ABL genetic domain now located within chromosome 22 and codes for a mutant tyrosine kinase also known as BCR-ABL. Under normal circumstances tyrosine kinase proteins respond to external cellular messaging proteins, and ultimately initiate a series of reactions that culminate in cellular replication. Conversely, BCR-ABL is constitutively active, meaning it does not require activation by the aforementioned cellular messaging proteins in order to stimulate cellular replication. This results in acceleration of cell division, an inhibition of DNA repair, overall genomic instability, and the fatal blast crisis characteristic of chronic myelogenous leukemia. The animation progresses to introduce Gleevec (imatinib), the first in a class of drugs that specifically target and competively inhibit the ATP binding site on BCR-ABL tyrosine kinase. This prevents the ABL domain from phosphorylating the tyrosine residue, and as a result preventing the proliferation of hematopoietic cells that express BCR-ABL. Therapy with imatinib results in a dramatic reduction of tumor clone cells and the occurrence of blast crisis', through targeted drug treatment which leaves health cells unscathed.




Created by:

Nelson Caetano
Class of 2007
Pharmacy




Dr. Bongsup Cho
Professor of Biomedical and Pharmaceutical Sciences
College of Pharmacy

Category:

Film & Animation

Tags:

• Gleevec
• Glivec
• mechanism
• of
• Action
• Drug
• Chronic
• Myologenous
• Leukemia
• Cancer
• URI
• animation

[um02122]

very impressive, could you tell me what program(s) used the creator of this animation?

[URIanimation]

We used Maya for the animation, zBrush for some of the modeling, and After Effects for the compositing

[Diastole2]

Fantastic visualization, very well done.

[WarriorInternationa1]

Karyotyping was done for a patient of suspected blood cancer. Chromosomal analysis indicated that there was an extra-long chromosome 9 and a shorter chromosome 22, called the Philadelphia chromosome. It is a diagnosis of chronic myeloid leukemia, a form of blood cancer in which a big portion of chromosome 22 is transferred to chromosome 9 and a small portion of 22 is transferred to chromosome 9.

[grantflashdance]

I posted my c-kit video to point out that imatinib binds to many other tyrosine kinases besides bcr-abl. Though it was designed against and tightly binds to bcr-abl with high affinity, a major success story of the drug is that it "promiscuously" binds to c-kit and PDGF-R TKs (and perhaps others) tightly as well. Since many growth-related TKs are deregulated in various proliferative diseases, Gleevec is a nice, well-tolerated shotgun approach to perhaps many cancers and related pathologies.

[pirejknf]

Great video.

[JordanHales]

cool vid and tech lol im impressed