Abstract
Ex-vivo studies have suggested that imatinib-resistance in chronic myeloid leukemia (CML) patients occurs despite adequate suppression of BCR-ABL activity. Whether BCR-ABL phosphorylation levels differ between imatinib-sensitive and -resistant patients is not known. We compared the phosphorylation of BCR-ABL in 54 previously untreated CML patients and 62 imatinib-resistant CML patients with progressive disease. Resistant patients had significantly lower levels of BCR-ABL, CrkL and AKT phosphorylation than previously untreated patients, but STAT5 phosphorylation showed no difference. These observations suggest that imatinib- resistance is not necessarily dependent on higher activity in BCR-ABL-dependent pathways, but is likely due to the activation of other pathways.
MeSH terms
-
Adaptor Proteins, Signal Transducing / metabolism*
-
Antineoplastic Agents / therapeutic use
-
Apoptosis / drug effects
-
Benzamides
-
Drug Resistance, Neoplasm*
-
Flow Cytometry
-
Fusion Proteins, bcr-abl / genetics
-
Fusion Proteins, bcr-abl / metabolism*
-
Gene Expression Regulation, Neoplastic / physiology
-
Humans
-
Imatinib Mesylate
-
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
-
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
-
Nuclear Proteins / metabolism*
-
Phosphorylation
-
Piperazines / therapeutic use*
-
Prognosis
-
Protein-Tyrosine Kinases / antagonists & inhibitors
-
Proto-Oncogene Proteins c-akt / metabolism*
-
Pyrimidines / therapeutic use*
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Reverse Transcriptase Polymerase Chain Reaction
-
STAT5 Transcription Factor / metabolism*
-
Signal Transduction / drug effects
-
Survival Rate
Substances
-
Adaptor Proteins, Signal Transducing
-
Antineoplastic Agents
-
Benzamides
-
CRKL protein
-
Nuclear Proteins
-
Piperazines
-
Pyrimidines
-
RNA, Messenger
-
STAT5 Transcription Factor
-
Imatinib Mesylate
-
Protein-Tyrosine Kinases
-
Fusion Proteins, bcr-abl
-
Proto-Oncogene Proteins c-akt