Imatinib resistance in chronic myeloid leukaemia caused by Bcr-Abl kinase domain and non-Bcr-Abl mutations: a comparison and review

Smith, Samuel (2017) Imatinib resistance in chronic myeloid leukaemia caused by Bcr-Abl kinase domain and non-Bcr-Abl mutations: a comparison and review. Australian Medical Student Journa, 8 (1). pp. 30-37.

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Abstract

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder caused by BCR-ABL1 igureusion encoding for a tyrosine kinase oncoprotein. Since the introduction of the tyrosine kinase inhibitor (TKI), imatinib, in 2000, CML survival rates have increased, to the point where life expectancy is equal to that of the general population. One obstacle patients face is imatinib resistance. Literature about resistance has mainly focussed on mutations in the Bcr-Abl kinase domain (KD), which have been well described. Areas that have not been as well established include the origin of KD mutations and resistance from mechanisms outside of KD mutations. This review focuses on how KD mutations arise and their mechanisms of resistance and the roles of BCR-ABL1 gene amplification, Erk1, and Lyn kinase in creating resistance outside of the KD. Experimental therapies to combat imatinib resistance are also mentioned. Using database searches to obtain the current literature, this review attempts to determine the current consensus on these topics and highlight areas where research could be beneficial. While the origin of KD-mutations and non-KD resistance is not entirely clear, the many possible causes that have been elucidated thus far have already paved the way for new therapies.

Item ID: 52182
Item Type: Article (Research - C1)
ISSN: 1837-1728
Keywords: leukaemia, cancer, chronic myeloid leukaemia, CML, chemotherapy, tyrosine kinase inhibitors, imatinib, drug resistance
Date Deposited: 05 Mar 2018 05:41
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111207 Molecular Targets @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111205 Chemotherapy @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111502 Clinical Pharmacology and Therapeutics @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920101 Blood Disorders @ 40%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 60%
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