| Literature DB >> 32103491 |
Cristina Jiménez1, Gloria G Chan1, Lian Xu1, Nickolas Tsakmaklis1, Amanda Kofides1, Maria G Demos1, Jiaji Chen1, Xia Liu1, Manit Munshi1, Guang Yang1, Jorge J Castillo1,2, Adrian Wiestner3, Ramón García-Sanz4, Steven P Treon1,2, Zachary R Hunter1,2.
Abstract
Ibrutinib is highly active in Waldenström macroglobulinaemia (WM) patients, but disease progression can occur due to acquired mutations in BTK, the target of ibrutinib, or PLCG2, the protein downstream of BTK. However, not all resistant patients harbour these alterations. We have performed a whole-exome sequencing study to identify alternative molecular mechanisms that can drive ibrutinib resistance. Our findings include deletions on chromosomes 6q, including homozygous deletions, and 8p, which encompass key regulators of BTK, MYD88/NF-κB, and apoptotic signalling. Moreover, we have identified recurring mutations in ubiquitin ligases, innate immune signalling, and TLR/MYD88 pathway regulators in ibrutinib-resistant WM patients.Entities:
Keywords: Waldenström macroglobulinemia; genomic alterations; ibrutinib; resistance; whole-exome sequencing
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Year: 2020 PMID： 32103491 PMCID： PMC7299825 DOI： 10.1111/bjh.16463
Source DB: PubMed Journal: Br J Haematol ISSN： 0007-1048 Impact factor: 6.998