Current opinion in hematology
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Curr. Opin. Hematol. · Jul 2002
ReviewMolecular mechanisms of resistance to STI571 in chronic myeloid leukemia.
Therapeutic use of the recently FDA-approved drug STI571 has been successful in the treatment of Philadelphia chromosome-positive leukemias. STI571 is a small molecule inhibitor with activity against BCR-ABL, the deregulated tyrosine kinase responsible for initiation and maintenance of the disease in the chronic phase of chronic myeloid leukemia (CML). ⋯ Studies investigating the molecular mechanisms of resistance to this novel compound have progressed rapidly and point to the continued importance of BCR-ABL in disease maintenance even at its latest stages. Here the authors review recent work aimed at elucidating the nature of STI51 resistance.
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It has long been believed that mammalian stem cells are irreversibly committed to the individual tissue in which they reside; however, several recent studies have challenged this assertion and suggest a remarkable plasticity of stem cells derived from various adult tissues. Hematopoietic stem cells have been central to this paradigm shift, and in this review, the authors discuss the recent advances in this rapidly growing field. Although several exciting findings in rodents have already led to clinical trials in humans, true stem cell plasticity has not rigorously been established in most, if not all, studies to date, and a number of issues remain unresolved. Large animal models should prove invaluable to the progress of the field.