Effects of Inactivating Ras-Converting Enzyme or Isoprenylcysteine Carboxyl Methyltransferases in the Pathogenesis of Chronic Myelogenous Leukemia
Abstract
The BCR-ABL fusion gene, the hallmark of CML, plays a causal role in the development of CML. The BCRABL tyrosine kinase inhibitors have been successfully used to treat patients with CML, but residual disease persists and drug resistance emerges. This clinical time bomb will have to be diffused in the not so distant future. Although BCR-ABL remains to be an attractive target for developing CML therapies, identifying and targeting additional essential components in the development of CML are important for overcoming resistance to BCR-ABL tyrosine kinase inhibitors and for eradicating leukemic cells. Substantial evidence indicates that Ras and Ras related proteins, which are commonly activated in human cancers, are critical mediators of BCR-ABL in leukemogenesis. Ras-converting enzyme (Rce1) and isoprenylcysteine carboxyl methyltransferase (Icmt) are two unique enzymes for Ras modifications that are critical for their functions. Targeted inactivation of Rce1 or Icmt is, therefore, an attractive strategy for the treatment of CML. The goal of this project is to determine whether targeted inactivation of Rce1 or Icmt could block BCR-ABL leukemogenesis. In the past funding period we have generated mice with conditional alleles of Rce1 or Icmt and used these mice to evaluate the importance of Rce1 in BCRABL leukemogenesis. Our preliminary results show that Rce1 plays an important role in the pathogenesis of CML.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2007
- Accession Number
- ADA472331
Entities
People
- Ruibao Ren
Organizations
- Brandeis University