Chronic Myelogenous Leukemia (CML) is a disease of the pluripotent stem cell which progresses through a series of stages (chronic, accelerated, and blast crisis) when cells become less regulated in their growth and differentiation properties. This clinical pattern is strongly correlated with a specific chromosomal abnormality, the Philadelphia chromosome-Ph?1?. Analysis at the DNA and RNA levels has demonstrated that the abl oncogene on chromosome 9 is altered by the translocation and abnormally expressed as a new larger mRNA species in cells from CML patients. These structural alterations result in the expression of a chimeric protein (called P210) composed of a portion of the abl sequences fused to sequences from an unidentified genetic region. Most importantly, this chimeric protein functions as a tyrosine kinase in vitro. This is a hallmark of the homologous viral form of the abl oncogene essential for its transforming activity. The P210 protein is expressed in all CML derived Ph?1? cell lines we have examined as well as multiple fresh clinical specimens from Ph?1? positive patients. This research will develop the nucleic acid structural information, recombinant expression vectors, serological reagents, and methodology to detect P210 in clinical material to aid diagnosis and follow the course of patients with this disease. (6)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040957-02
Application #
3181266
Study Section
(SSS)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095