Investigation of therapy resistance mechanisms in myeloid leukemia by protein profiling of bone marrow extracellular fluid.

In spite of the effective chronic myeloid leukemia (CML) therapy, a small percentage will fail on therapy and develop acute myeloid leukemia-like blast crisis. Understanding the underlying biology of therapy resistance is probably needed to develop better blood cancer therapy, and CML may be an ideal disease model for future therapy that targets resistance mechanisms. Cell-stromal interactions and dissection of the interstitial tissue fluid is a relatively new source for understanding the resistance mechanisms. Abdelhay's team have compared the proteome of bone marrow plasma in CML imatinib (Gleevec) responders and nonresponders. We discuss their findings of dysregulated redox and Wnt signaling in imatinib resistance, illustrating how powerful proteomics may be in the discovery of new therapeutic mechanisms.