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Leuk Lymphoma. 2008 Apr;49(4):604-9. doi: 10.1080/10428190801923212.

Clinical perspectives of concepts on neoplastic stem cells and stem cell-resistance in chronic myeloid leukemia.

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  • 1Division of Hematology & Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Austria. peter.valent@meduniwien.ac.at


In chronic myeloid leukemia (CML), neoplastic stem cells and/or their subclones exhibit resistance against BCR/ABL tyrosine kinase inhibitors (TKIs). Therefore, residual CML stem cells (subclones) in TKI-treated patients are a logical target of therapy, and their elimination is considered a major aim and clue in the development of curative treatment approaches. A number of different mechanisms may underly resistance of CML stem cells against TKIs and other targeted or/and conventional drugs, including stem cell quiescence, expression of drug-transporters, stem cell plasticity, BCR/ABL mutations, overexpression of BCR/ABL and BCR/ABL-independent signalling- and survival-molecules. In this article, possibilities to overcome stem cell resistance in CML by exploiting knowledge on molecular mechanisms that underly the 'stem cell escape' from drug therapy are discussed.

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