Multidrug resistance in chronic myeloid leukemia

References (1)

1. Predictive response to therapy et al. 2009 miR-31 downregulation miRNA E2F2 Predictive response to therapy Rokah et al., 2012 miR-564 downregulation miRNA E2F3, Akt2 Predictive response to therapy Rokah et al., 2012 miR-155 downregulation miRNA E2F2, cyclin D1, K-ras, PIK3R1, SOS1 to therapy Rokah et al., 2012 ncRNA: noncoding RNA, N/A: not available. of disease. It was also documented that CD34+ leukemia stem cells are insensitive to imatinib and dasatinib, and therefore these applications would be ineffective unless directly targeting leukemic stem cells to induce apoptosis (Graham et al., 2002; Hu et al., 2006). Furthermore, the existence of CSCs is reported in other solid tumors. Breast cancer is the first solid tumor in which CSCs with the CD44+/CD24– surface marker was identified (Al-Hajj et al., 2003). Many CSCs have been identified and characterized for brain tumors, lung cancer, colon cancer, pancreas cancer, and prostate cancer so far (Singh et al., 2003; Kim et al., 2005; Ricci-Vitiani et al., 2007; Li et al., 2009; Goldstein et al., 2010). Signaling pathways such as BMI-1, Notch, and Hedgehog have important roles in stemness and also regulate the activities of CSCs. After developing mice deficient in β-catenin in the hematopoietic cells, HSC and CSCs were isolated. Results showed a lack of the capacity for self-renewal, indicating the requirement of Wnt signaling in CSC maintenance (Zhao et al., 2007). The Hedgehog signaling pathway is as important as the Wnt signaling pathway in terms of stem cell regulation and embryonic formation. Suppression of Smoothened (Smo) decreased the triggering of CML stem cells in human (Zhao et al., 2009). In addition, it was shown that there is crosstalk among Sonic Hedgehog, Hox, and Notch signaling to induce the potential of CSCs (Sengupta et al., 2007). Since potential drugs target cancer cells instead of CSCs, drug resistance remains the major problem during treatment. In order to prevent the production of new cancer cells by cancer stem cells and to overcome reversal of resistance, recent studies have focused on targeting CSCs. It was agreed that imatinib and other TKIs could not be effective on cancer stem cells due to disease relapse in the long-term (Corbin et al., 2011; Perl and Carroll, 2011). Distinguishing cancer stem cells from normal stem cells is another crucial point for the success of treatment. It is possible to eliminate normal stem cells by targeting the B-lymphoid kinase gene (Blk), which act