Upload
lillith-frost
View
48
Download
2
Tags:
Embed Size (px)
DESCRIPTION
Retinoic Acid Receptor Alpha and Acute Promyelocytic Leukemia. Nidhi Thapar April 1, 2004. Acute Promyelocytic Leukemia. Proliferation of immature blood cells 10,600 new cases of AML each year. Most patients with APL achieve a complete remission when treated (with ATRA). - PowerPoint PPT Presentation
Citation preview
Retinoic Acid Receptor Alpha
and
Acute Promyelocytic Leukemia
Nidhi ThaparApril 1, 2004
Acute Promyelocytic Leukemia
• Proliferation of immature blood cells
• 10,600 new cases of AML each year.
• Most patients with APL achieve a complete remission when treated (with ATRA)
http://my.webmd.com/http://www.cancer.gov
Retinoic Acid
• Member of a family called retinoids, derived from Vitamin A
• Enters the nucleus and binds to receptors, initiating transcription factors
http://www.ncbi.nlm.nih.gov/
Signalingby Retinoic Acid
http://www.ncbi.nlm.nih.gov/
RARα normal function
• In the absence of RA RAR/RXR recruits repression complex
• Results in transcriptional repression
Lin, et al.
RARα normal function
• Presence of RA induces the dissociation of repression complex
• Acetylation of histones leads to promoter clearance which activates transcription
Lin, et al.
Chromosome Translocation Results in
PML• Translocation occurs between
chromosomes 15 and 17• As a result, an abnormal protein
product is produced, PML/RARα
http://www.genetics.com.au
X- RARα
• Leads to differentiation blockage
• Activates target genes leading to overexpression
http://www.ncbi.nlm.nih.gov/
Knock-out Mice
• RARα-/ RARα- had no effect on phenotype
• Triple mutants hard to make
http://mbbnet.umn.edu/firsts/mouse.jpeg&imgrefurl
Treatment
• High doses of RA in combination with chemotherapy
Lin, et al.
HDAC inhibitors
• HDAC inhibitors are therapeutic target
• Works well in combination with ATRA
• Potent inducers of growth arrest, differentiation and apoptosis
thank you