Open AccessMechanisms of resistance to targeted therapies in chronic lymphocytic leukemia
Author(s) -
Sutton LesleyAnn
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/hs9.0000000000000240
Subject(s) - ibrutinib , idelalisib , venetoclax , bruton's tyrosine kinase , chronic lymphocytic leukemia , medicine , cancer research , breakpoint cluster region , leukemia , acquired resistance , oncology , immunology , cancer , tyrosine kinase , receptor
Although durable remissions are observed in many patients treated with these agents, including those with poor risk features, it is becoming apparent that some patients will ultimately relapse. Potential acquired resistance mechanisms identified to date include BTK (C481) and PLCG2 mutations in patients undergoing treatment with ibrutinib and a recurrent mutation at codon V101 within the BCL2 gene in patients treated with venetoclax. The observation that some patients with acquired clinical resistance have extremely low allelic frequencies of BTK, PLCG2 or BCL2 mutations or, in some instances are absent for mutations in these genes, indicates that additional (epi)genetic aberrations must play a role in acquired resistance to novel agents.