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Current Hematologic Malignancy Reports

, Volume 14, Issue 5, pp 395–404 | Cite as

Molecular Mechanisms of Resistance to Tyrosine Kinase Inhibitors

  • Marjan YaghmaieEmail author
  • Cecilia CS Yeung
Molecular Testing and Diagnostics (J Khoury, Section Editor)
  • 221 Downloads
Part of the following topical collections:
  1. Topical Collection on Molecular Testing and Diagnostics

Abstract

Purpose of Review

Chronic myeloid leukemia (CML) patients with constitutive activity of BCR-ABL1 oncoprotein frequently derive significant clinical benefits from tyrosine kinase inhibitors (TKIs). Point mutations in the ABL1 kinase domain (KD) are an important mechanism of TKI resistance in CML. In this review, we present molecular mechanisms of TKI resistance paying particular attention to drug resistance which allows for a survival advantage in CML.

Recent Findings

Sensitive disease monitoring is a required standard of care for management of CML. Screening of these mutations fail to explain 20–40% of resistant cases where activation of different survival pathways must be the main reason for resistance.

Summary

Eliminating TKI resistance appears to be the most successful therapeutic way to decrease leukemic disease burden and potentiate cure. Advances on novel strategies for identifying and confronting drug resistance are rapidly altering management of CML that are resistant to TKI and expanding the landscape of available therapies.

Keywords

Chronic myeloid leukemia Molecular mechanism Tyrosine kinase inhibitor Resistance mutations 

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Yeung reports grants from OBI Pharmaceuticals and Pfizer outside the submitted work. Dr. Yaghmaie declares no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. 1.Hematology, Oncology and Stem Cell Transplantation Research CenterTehran University of Medical SciencesTehranIran
  2. 2.Fred Hutchinson Cancer Research Center, Clinical Research DivisionSeattleUSA
  3. 3.Department of PathologyUniversity of WashingtonSeattleUSA

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