Mechanisms of Disease Progression and Resistance to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: An Update
Abstract
:1. Introduction
2. Overview of Known Mechanisms Underlying Progression to BP
3. BCR-ABL1 and Genomic Instability
4. Additional Chromosomal Abnormalities
5. Gene Mutations and Submicroscopic Genetic Abnormalities
6. Non Genomic Loss of Tumor-Suppressor Function
7. Differentiation Arrest
8. Methylation Changes
9. Perturbations in RNA Transcription, Editing and Translation
10. The Role of MicroRNAs
11. Metabolic Changes
12. TKI Resistance and LSC Persistence: Two Sides of the Same Coin?
13. Conclusions and Future Perspectives
Funding
Conflicts of Interest
References
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Gene/Pathway | Ref | Druggable? |
---|---|---|
PI3K/AKT/mTOR | Burchert, Leukemia 2005 [135] | PI3K/mTOR inhibitors |
Lyn | Wu et al., Blood 2008 [136] | Src inhibitors |
Autophagy | Bellodi et al., J Clin Invest 2009 [137] | hydroxychloroquine |
SHP-1 | Esposito et al., Blood 2011 [138] | X |
SIRT1 | Wang et al., Oncogene 2013 [139] | selisistat |
PRKCH | Ma et al., Sci Transl Med 2014 [140] | MEK inh (trametinib) + Imatinib |
STAT3 | Eiring et al., Leukemia 2015 [141] | BP-5-087 |
CRM1/XPO1/RAN | Khorashad et al., Blood 2015 [142] Walker et al., Blood 2016 [143] | selinexor |
JAK2 | Chakraborty et al., Genes Cancer 2016 [144] | ruxolitinib |
FOXO1 | Wagle et al., Leukemia 2016 [145] | PI3K inhibitors |
EZH2 | Scott et al., Cancer Discov 2016 [146] | EZH2 inhibitors |
Wnt/b catenin | Eiring et al., Leukemia 2015 [141], Zhou et al., Leukemia 2017 [147] | C82 |
MS4A3 | Eiring et al., ASH 2017 [148] | X |
PFKFB3 | Zhu et al., Oncogene 2018 [149] | PFK-158 |
Various miRNAs | X |
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Bavaro, L.; Martelli, M.; Cavo, M.; Soverini, S. Mechanisms of Disease Progression and Resistance to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: An Update. Int. J. Mol. Sci. 2019, 20, 6141. https://doi.org/10.3390/ijms20246141
Bavaro L, Martelli M, Cavo M, Soverini S. Mechanisms of Disease Progression and Resistance to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: An Update. International Journal of Molecular Sciences. 2019; 20(24):6141. https://doi.org/10.3390/ijms20246141
Chicago/Turabian StyleBavaro, Luana, Margherita Martelli, Michele Cavo, and Simona Soverini. 2019. "Mechanisms of Disease Progression and Resistance to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: An Update" International Journal of Molecular Sciences 20, no. 24: 6141. https://doi.org/10.3390/ijms20246141