CDKN2A (5/7, 71%) was frequently deleted, and the deletion was only observed in the ibrutinib-resistant tumors (p = 0.010). The RNA-seq analysis identified a total of 63 protein-coding genes as the most differentially expressed genes (DEGs) between the ibrutinib-resistant and -sensitive ...
catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant A Hamasy1,4, Q Wang1,4, KEM Blomberg1, DK Mohammad1, L Yu2, M Vihinen3, A Berglöf1 and CIE Smith1 Irreversible Bruton tyrosine kinase (BTK) inhibitors, ibrutinib and acalabrutinib have demonstrated ...
Jinseok Hwang, Yuqin Song, Wanli Liu& Yu Rao Cell Research28,779–781 (2018)Cite this article 18kAccesses 237Citations 12Altmetric Metrics Dear Editor, Non-Hodgkin’s lymphoma (NHL) is a type of cancer that mainly develops from B-cell malignancies, causing 231,400 deaths in 2015 globally...
Summary Ibrutinib is highly active in Waldenstrm 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...
The Bruton Kinase (BTK) inhibitor, ibrutinib, pioneered a paradigm shift in the treatment of chronic lymphocytic leukemia (CLL), especially in high-risk cytogenetic groups. Despite its transformative efficacy, it can be associated with a high discontinuation rate, particularly in the community setting...
However, the bottleneck of ibrutinib resistance has caused widespread concerns, necessitating the exploration of novel targets. MethodsSingle-cell RNA sequencing (scRNA-seq) was used to characterize the heterogeneity of ibrutinib-sensitive (IBS) and -resistant (IBR) CLL patients and single-cell stem...
LOXO-305: Targeting C481S Bruton Tyrosine Kinase in Patients with Ibrutinib-Resistant CLLClinical success with the targeted Bruton Tyrosine Kinase (BTK) inhibitors ibrutinib and acalabrutinib has greatly improved the outcome of patients with relapsed chronic lymphocytic leukemia (CLL). However toxic ...
The ROR1 inhibitor induced apoptosis in ibrutinib-resistant CLL cells to the same degree as in ibrutinib-sensitive cells and dephosphorylated ROR1. This was also noted in one patient who became resistant to both ibrutinib and the Bcl-2 inhibitor venetoclax. The combination of ROR1 inhibitor and...
Disclosed are methods of treating an ibrutinib-resistant disease in a mammal with a compound of Formula (I): wherein R is described herein. In certain embodiments, a compound of Formula (I) inhibits the activity of a variant Btk, providing a method of treating ibrutinib-resistant diseases, ...
Early reappearance of intraclonal proliferative subpopulations in ibrutinib-resistant chronic lymphocytic leukemiaChronic lymphocytic leukaemiaTranslational researchThe Bruton's tyrosine kinase (BTK) inhibitor ibrutinib represents an effective strategy for treatment of chronic lymphocytic leukemia (CLL), nevertheless...