The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy

DSpace/Manakin Repository

The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy

Citable link to this page

 

 
Title: The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy
Author: Landau, Dan A.; Sun, Clare; Rosebrock, Daniel; Herman, Sarah E. M.; Fein, Joshua; Sivina, Mariela; Underbayev, Chingiz; Liu, Delong; Hoellenriegel, Julia; Ravichandran, Sarangan; Farooqui, Mohammed Z. H.; Zhang, Wandi; Cibulskis, Carrie; Zviran, Asaf; Neuberg, Donna S.; Livitz, Dimitri; Bozic, Ivana; Leshchiner, Ignaty; Getz, Gad; Burger, Jan A.; Wiestner, Adrian; Wu, Catherine J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Landau, D. A., C. Sun, D. Rosebrock, S. E. M. Herman, J. Fein, M. Sivina, C. Underbayev, et al. 2017. “The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy.” Nature Communications 8 (1): 2185. doi:10.1038/s41467-017-02329-y. http://dx.doi.org/10.1038/s41467-017-02329-y.
Full Text & Related Files:
Abstract: Treatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents. To define the evolutionary dynamics induced by targeted therapy in CLL, we perform serial exome and transcriptome sequencing for 61 ibrutinib-treated CLLs. Here, we report clonal shifts (change >0.1 in clonal cancer cell fraction, Q < 0.1) in 31% of patients during the first year of therapy, associated with adverse outcome. We also observe transcriptional downregulation of pathways mediating energy metabolism, cell cycle, and B cell receptor signaling. Known and previously undescribed mutations in BTK and PLCG2, or uncommonly, other candidate alterations are present in seventeen subjects at the time of progression. Thus, the frequently observed clonal shifts during the early treatment period and its potential association with adverse outcome may reflect greater evolutionary capacity, heralding the emergence of drug-resistant clones.
Published Version: doi:10.1038/s41467-017-02329-y
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736707/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34651940
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters