Mechanisms of Disease Persistence in Chronic Myelogenous Leukemia (CML)

摘要: Abstract : Disease persistence is the main issue faced by CML patients on therapy with imatinib and eradication of persistent malignant cells will be critical for long-term success kinase inhibitor therapy. Mechanisms underlying acquired resistance to have been extensively studied manner which mutations Bcr-Abl domain can reduce or eliminate sensitivity has well characterized. in responding patients, contrast,is still poorly understood. We sought identify characterize hematopoietic stem responsible disease explore their mechanisms resistance. Using vitro culture primary progenitor cells, we identified both quiescent cycling capable surviving presence imatinib. observed inhibition tyrosine phosphorylation phenotypically-defined culture, suggesting a independent mechanism survival. To apply information gained from cell populations treated attempted isolate positive cytogenetic remission. Although may reside within compartment, techniques enrichment did not lead cells. therefore explored Bcr-Abl-specific detection facilitate these studies, including creation junction-specific antibody, development mRNA molecular beacon analysis potential markers The detailed samples technically challenging, but essential an understanding allow identification novel drug targets methods sensitize resistant alternative inhibitors.