Resistance to imatinib in chronic myeloid leukemia and therapeutic approaches to circumvent the problem.

Content Provider	Semantic Scholar
Author	Breccia, Massimo Alimena, Giuliana
Copyright Year	2009
Abstract	The majority of patients with chronic phase chronic myeloid leukaemia (CP-CML) treated with imatinib achieves cytogenetic disease remission. Molecular monitoring for residual disease has prognostic significance: rising BCR-ABL levels may provide earliest indication that a patient has become resistant to treatment. The emergence of resistance to imatinib has dampened the enthusiasm for this drug. The most common cause of resistance is the selection of leukemic clones mutated in ABL kinase domain due to amino acid substitutions with prevention of appropriate binding of the drug. Amplification and over-expression of BCR-ABL, acquired cytogenetic aberrations and modulation of drug efflux or influx transporters have been reported. These observations have established the rationale for the creation of new compounds that have been explored in clinical trials. This review will discuss the underlying mechanisms of imatinib-resistance and new strategies to avoid and overcome this phenomenon.
Starting Page	421
Ending Page	434
Page Count	14
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.benthamscience.com/cdtchd/sample/chddt9-1/0003X.pdf
PubMed reference number	19275574v1
Volume Number	9
Issue Number	1
Journal	Cardiovascular & hematological disorders drug targets
Language	English
Access Restriction	Open
Subject Keyword	Abetalipoproteinemia Amino Acid Substitution Amino Acids Chromosome Aberrations Drug Efflux Escalation Forecast of outcome Fusion Proteins, bcr-abl Leukemia, Myeloid, Chronic-Phase Mutation Myeloid Leukemia Myeloid Leukemia, Chronic Patients Propionibacterium acnes Residual Tumor Reverse Transcriptase Polymerase Chain Reaction abl Oncogene bosutinib dasatinib imatinib nilotinib
Content Type	Text
Resource Type	Article