Format

Send to

Choose Destination
Blood. 2009 Feb 19;113(8):1619-30. doi: 10.1182/blood-2008-03-144790. Epub 2008 Sep 30.

Molecular biology of bcr-abl1-positive chronic myeloid leukemia.

Author information

1
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. aquintas@mdanderson.org

Abstract

Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a malignancy defined by a unique molecular event, the BCR-ABL1 oncogene. Decades of research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML have culminated in the development of highly efficacious therapeutics that, like imatinib mesylate, target the oncogenic kinase activity of BCR-ABL1. In recent years, most research efforts in CML have been devoted to developing novel tyrosine kinase inhibitors (TKIs) as well as to elucidating the mechanisms of resistance to imatinib and other TKIs. Nonetheless, primordial aspects of the pathogenesis of CML, such as the mechanisms responsible for the transition from chronic phase to blast crisis, the causes of genomic instability and faulty DNA repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in TKI resistance and CML progression, or the cross-talk between BCR-ABL1 and other oncogenic signaling pathways, still remain poorly understood. Herein, we synthesize the most relevant and current knowledge on such areas of the pathogenesis of CML.

PMID:
18827185
PMCID:
PMC3952549
DOI:
10.1182/blood-2008-03-144790
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center