Hematology
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NIH Career Development Awards are designed to provide outstanding, clinically trained professionals with salary support and protected time to pursue a course of intensive, mentored research experience necessary to achieve full scientific independence. The ideal candidate for a career development award is a health scientist nearing the completion of postdoctoral training or in the early years of a faculty position. The K series of NIH awards provide several options for mentored training that are appropriate for investigators interested in laboratory or clinical investigation in the biologic and medical sciences.
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The emergence of resistance to imatinib has become a significant problem despite the remarkable clinical results achieved with this tyrosine kinase inhibitor in the treatment of chronic myeloid leukaemia. The most common cause of imatinib resistance is the selection of leukemic clones with point mutations in the Abl kinase domain. These mutations lead to amino acid substitutions and prevent the appropriate binding of imatinib. ⋯ A multitude of novel agents have been developed and have shown in vitro and in vivo efficacy in overcoming imatinib resistance. In this review, we will discuss the current status of the ATP-competitive and non-ATP-competitive Bcr-Abl tyrosine kinase inhibitors. We will also describe inhibitors acting on targets found in signaling pathways downstream of Bcr-Abl, such as the Ras-Raf-mitogen-activated protein kinase and phosphatidylinositol-3 kinase-Akt-mammalian target of rapamycin pathways, and targets without established links with Bcr-Abl.