Phosphorylation levels of BCR-ABL, CrkL, AKT and STAT5 in imatinib-resistant chronic myeloid leukemia cells implicate alternative pathway usage as a survival strategy.

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.
Authors	Iman Jilani, Hagop Kantarjian, Mercedes Gorre, Jorge Cortes, Oliver Ottmann, Kapil Bhalla, Francis J Giles, Maher Albitar
Journal	Leukemia research (Leuk Res) Vol. 32 Issue 4 Pg. 643-9 (Apr 2008) ISSN: 0145-2126 [Print] England
PMID	17900686 (Publication Type: Journal Article)
Chemical References	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
Topics	Adaptor Proteins, Signal Transducing (metabolism) Antineoplastic Agents (therapeutic use) Apoptosis (drug effects) Benzamides Drug Resistance, Neoplasm Flow Cytometry Fusion Proteins, bcr-abl (genetics, metabolism) Gene Expression Regulation, Neoplastic (physiology) Humans Imatinib Mesylate Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, 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, metabolism) Reverse Transcriptase Polymerase Chain Reaction STAT5 Transcription Factor (metabolism) Signal Transduction (drug effects) Survival Rate

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