Format

Send to

Choose Destination
Leukemia. 2008 May;22(5):898-904. doi: 10.1038/leu.2008.71. Epub 2008 Mar 20.

Rac GTPases as key regulators of p210-BCR-ABL-dependent leukemogenesis.

Author information

1
Division of Experimental Hematology, Cincinnati Children's Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Abstract

Chronic myelogenous leukemia (CML) is a malignant disease characterized by expression of p210-BCR-ABL, the product of the Philadelphia chromosome. Survival of CML patients has been significantly improved with the introduction of tyrosine kinase inhibitors that induce long-term hematologic remissions. However, mounting evidence indicates that the use of a single tyrosine kinase inhibitor does not cure this disease due to the persistence of p210-BCR-ABL at the molecular level or the acquired resistance in the stem cell compartment to individual inhibitors. We have recently shown in a murine model that deficiency of the Rho GTPases Rac1 and Rac2 significantly reduces p210-BCR-ABL-mediated proliferation in vitro and myeloproliferative disease in vivo, suggesting Rac as a potential therapeutic target in p210-BCR-ABL-induced disease. This target has been further validated using a first-generation Rac-specific small molecule inhibitor. In this review we describe the role of Rac GTPases in p210-BCR-ABL-induced leukemogenesis and explore the possibility of combinatorial therapies that include tyrosine kinase inhibitor(s) and Rac GTPase inhibitors in the treatment of CML.

PMID:
18354486
PMCID:
PMC4464749
DOI:
10.1038/leu.2008.71
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center