Research in Analysis of MLL Translocation
and Fusion Genes
 My research focuses on specific, recurring gene changes that lead to
certain subtypes of leukemia. Leukemia cells taken from patients who have
been diagnosed with a specific subtype of leukemia will often show a
consistent genetic abnormality, such as an exchange of DNA between two
different chromosomes. These chromosome rearrangements can cause abnormal
expression of genes near the breaks in each chromosome or creation of
fusion genes composed of parts of genes from each chromosome.
Both types of
genetic deregulation can lead to leukemia. Approximately 70 percent of infants
and children less than one year of age who are diagnosed with acute
leukemia often show chromosome rearrangements which form gene fusions
involving the MLL gene on chromosome 11. MLL can fuse to more than 50
different genes on different chromosomes in these leukemias. My current
research focuses on:
- Determining the mechanism of chromosome breakage
and rearrangement involving MLL and
- Determining the role of the MLL
fusion genes in development of leukemia.
Research Developments
- We have confirmed topoisomerase II induced in vitro cleavage of an MLL-translocation partner gene (AF4) in the reported translocation breakpoint region. Cleavage in this gene has not been reported previously. We are currently mapping the cleavage point. Data to be presented at the annual AACR meeting in April 2007 at an undergraduate research caucus. We have made progress in the ChIP analysis of the MLL breakpoint region. Repeated analyses show topo II binding in the extreme 5' region of the reported MLL breakpoint. This confirms electrophoretic mobility shift data from 2 years ago and may constiute convincing data for a short publication. RNAi studies continue in two cell lines. Although we can achieve 80+ percent knockdown of control genes, both the MLL-AF4 and MLL-AF6 fusion mRNAs appear to be resistant to knockdown with the siRNAs and conditions we are currently using. New experiements will pool siRNAs currently used individually.
Conferences and Meetings
- One-day grant-writing workshop by David Morrison, Lincoln, NE. October 17, 2006.
Student Researchers
- Students employed: 3
- Students receiving credit: Unknown
- Students using labs and equipment: 15
Student Presentations or Posters
- Last presentation: In Vitro DNA Clevage By DNA Topoisomerase II Inhibitors In the AF4 Gene Translocation Breakpoint Region. Ashley Olander and Heidi J. Super, Proceedings National IDeA Symposium of Biomedical Research Excellence, July 2006.
Events of Significance
- Oct. 10, 2006, Minot Daily News article entitled: Following up some prizewinning research: MSU biology researchers benefit from Nobel-winning techniques
Links
|
|
|
|
