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Chronic Myeloid Leukemia: Advances in Understanding Disease Biology and Mechanisms of Resistance to Tyrosine Kinase Inhibitors

  • Chronic Myeloid Leukemias (E Jabbour, Section Editor)
  • Published:
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Abstract

The successful implementation of tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML) remains a flagship for molecularly targeted therapy in cancer. This focused review highlights critical elements of the underlying biology of CML and provides a summary of the molecular mechanisms that lead to TKI resistance: BCR-ABL1 mutation-based resistance and therapy escape through alternative pathway activation despite inhibition of BCR-ABL1 tyrosine kinase activity. We direct attention to the most current manifestations of these issues, including emergence of pan-TKI-resistant BCR-ABL1 compound mutants, new strategies for identification and therapeutic targeting of alternative pathways, and the exciting, controversial topic of cessation of TKI therapy leading to durable treatment-free remissions for a subset of patients. Further gains in our understanding of the biology of Philadelphia chromosome-positive (Ph-positive) leukemia and mechanisms of resistance to BCR-ABL1 TKIs will benefit patients and also provide a blueprint for similar discovery in other cancers.

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Conflict of Interest

Dr. Christopher A. Eide declares that he has no conflict of interest. Dr. Thomas O’Hare declares that he has no conflict of interest.

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Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, OR, USA

    Christopher A. Eide

  2. Howard Hughes Medical Institute, Portland, OR, USA

    Christopher A. Eide

  3. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Thomas O’Hare

  4. Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, UT, USA

    Thomas O’Hare

  5. 2000 Circle of Hope, Room 4264, Salt Lake City, UT, 84112, USA

    Thomas O’Hare

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  1. Christopher A. Eide
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Correspondence to Thomas O’Hare.

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This article is part of the Topical Collection on Chronic Myeloid Leukemias

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Eide, C.A., O’Hare, T. Chronic Myeloid Leukemia: Advances in Understanding Disease Biology and Mechanisms of Resistance to Tyrosine Kinase Inhibitors. Curr Hematol Malig Rep 10, 158–166 (2015). https://doi.org/10.1007/s11899-015-0248-3

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