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Current Hematologic Malignancy Reports

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01-12-2019 | Chronic Myeloid Leukemia | Chronic Myeloid Leukemias (G Saglio, Section Editor)

The Hidden Pathogenesis of CML: Is BCR-ABL1 the First Event?

Authors: Naranie Shanmuganathan, Susan Branford

Published in: Current Hematologic Malignancy Reports | Issue 6/2019

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.

Summary

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.

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Title: The Hidden Pathogenesis of CML: Is BCR-ABL1 the First Event?
Authors: Naranie Shanmuganathan
Susan Branford
Publication date: 01-12-2019
Publisher: Springer US
Keyword: Chronic Myeloid Leukemia
Published in: Current Hematologic Malignancy Reports / Issue 6/2019
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI: https://doi.org/10.1007/s11899-019-00549-1

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