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Type: Journal article
Title: The hidden pathogenesis of CML: is BCR-ABL1 the first event?
Author: Shanmuganathan, N.
Branford, S.
Citation: Current Hematologic Malignancy Reports, 2019; 14(6):481-491
Publisher: Springer
Issue Date: 2019
ISSN: 1558-8211
Statement of
Naranie Shanmuganathan, Susan Branford
Abstract: PURPOSE OF REVIEW:Identification of the BCR-ABL1 fusion oncogene in patients diagnosed with chronic myeloid leukemia (CML) led to the development of targeted therapy responsible for the dramatic survival benefits observed in the past two decades. However, despite these revolutionary findings, there remains marked disparity in patient outcomes. Why do some patients present de novo while others evolve to the more aggressive stages of CML? Why can select patients successfully discontinue therapy as part of a treatment-free remission attempt whereas others fail to meet specific molecular milestones? RECENT FINDINGS:BCR-ABL1 kinase mutations are only identified in approximately 50% of patients with poor responses and disease progression, suggesting the presence of alternative resistance mechanisms. Numerous institutions have identified the presence of additional genomic events in addition to BCR-ABL1 with the increasing availability of next-generation sequencing. We explore the potential pathways and events that may cooperate with BCR-ABL1 to answer these questions but also challenge the fundamental tenet that BCR-ABL1 is always the sole event initiating CML.
Keywords: TKI; deep molecular responses; drug toxicity; treatment-free remission
Rights: © Springer Science+Business Media, LLC, part of Springer Nature 2019
DOI: 10.1007/s11899-019-00549-1
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