Mutational landscape of chronic myeloid leukemia: more than a single oncogene leukemia. Issue 9 (29th July 2021)

• Record Type: Journal Article
• Authors: Adnan-Awad, Shady; Kankainen, Matti; Mustjoki, Satu
• Is Part Of: Leukemia & lymphoma. Volume 62:Issue 9(2021)
• Page Start: 2064
• Page End: 2078
• Publication Date: 2021-07-29
• Subjects: Chronic myeloid leukemia -- blast phase -- somatic mutations -- risk stratification -- personalized medicine; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2021.1894652
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: The BCR-ABL1 fusion gene, which causes aberrant kinase activity and uncontrolled cell proliferation, is the hallmark of chronic myeloid leukemia (CML). The development of tyrosine kinase inhibitors (TKI) that target the BCR-ABL oncoprotein has led to dramatic improvement in CML management. However, some challenges remain to be addressed in the TKI era, including patient stratification and the selection of frontline TKIs and CML progression. Additionally, with the emerging goal of treatment-free remission (TFR) in CML management, biomarkers that predict the outcomes of stopping TKI remain to be identified. Notably, recent reports have revealed the power of genome screening in understanding the role of genome aberrations other than BCR-ABL1 in CML pathogenesis. These studies have discovered the presence of disease-phase specific mutations and linked certain mutations to inferior responses to TKI treatment and CML progression. A personalized approach that incorporates genetic data in tailoring treatment strategies has been successfully implemented in acute leukemia, and it represents a promising approach for the management of high-risk CML patients. In this article, we will review current knowledge about the mutational profile in different phases of CML as well as patterns of mutational dynamics in patients having different outcomes. We highlight the effects of somatic mutations involving certain genes (e.g. epigenetic modifiers) on the outcomes of TKI treatment. We also discuss the potential value of incorporating genetic data in treatment decisions and the routine care of CML patients as a future direction for optimizing CML management.