Research ArticleCancer

Tyrosine kinase inhibitor–induced CD70 expression mediates drug resistance in leukemia stem cells by activating Wnt signaling

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Science Translational Medicine  29 Jul 2015:
Vol. 7, Issue 298, pp. 298ra119
DOI: 10.1126/scitranslmed.aab1740

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A one-two punch for CML

Chronic myelogenous leukemia (CML) is classically associated with the pathogenic BCR-ABL1 translocation, which can be targeted by treatment with imatinib and other tyrosine kinase inhibitors. Unfortunately, these treatments do not eradicate leukemia stem cells, and many patients eventually relapse. Now, Riether et al. have identified a mechanism for treatment resistance in this cancer, showing that it can be caused by up-regulation of CD70 and resulting up-regulation of the Wnt pathway. In addition, the authors showed that this resistance can be successfully blocked by inhibiting the activity of CD70, suggesting a clinical application for this finding.

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