Oncotarget

Reviews:

BCR: a promiscuous fusion partner in hematopoietic disorders

Malalage N. Peiris, Fangda Li, Daniel J. Donoghue

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Oncotarget. 2019; 10:2738-2754. https://doi.org/10.18632/oncotarget.26837

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Abstract

Malalage N. Peiris1, Fangda Li1 and Daniel J. Donoghue1,2

1 Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA

2 UCSD Moores Cancer Center, University of California San Diego, La Jolla, California, USA

Correspondence to:

Daniel J. Donoghue, email: ddonoghue@ucsd.edu

Keywords: oncogenic fusion protein; chromosomal translocation; leukemia; breakpoint cluster region; RTK

Received: February 01, 2019     Accepted: March 23, 2019     Published: April 12, 2019

ABSTRACT

Considerable advances have been made in our understanding of the molecular basis of hematopoietic cancers. The discovery of the BCR-ABL fusion protein over 50 years ago has brought about a new era of therapeutic progress and overall improvement in patient care, mainly due to the development and use of personalized medicine and tyrosine kinase inhibitors (TKIs). However, since the detection of BCR-ABL, BCR has been identified as a commonly occurring fusion partner in hematopoietic disorders. BCR has been discovered fused to additional tyrosine kinases, including: Fibroblast Growth Factor Receptor 1 (FGFR1), Platelet-derived Growth Factor Receptor Alpha (PDGFRA), Ret Proto-Oncogene (RET), and Janus Kinase 2 (JAK2). While BCR translocations are infrequent in hematopoietic malignancies, clinical evidence suggests that patients who harbor these mutations benefit from TKIs and additional personalized therapies. The improvement of further methodologies for characterization of these fusions is crucial to determine a patient’s treatment regimen, and optimal outcome. However, potential relapse and drug resistance among patients’ highlights the need for additional treatment options and further understanding of these oncogenic fusion proteins. This review explores the mechanisms behind cancer progression of these BCR oncogenic fusion proteins, comparing their similarities and differences, examining the significance of BCR as a partner gene, and discussing current treatment options for these translocation-induced hematopoietic malignancies.


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