Clonal Evolution In Patients With Chronic Lymphocytic Leukemia (CLL) Developing Resistance To BTK Inhibition
Burger JA, Landau D, Hoellenriegel J et al.
Key Points:
Examine etiologies of resistance to BTK inhibition by CLL cells who initially responded to ibrutinib and later progressed.
Pretreatment molecular profile: patient 1-TP53 and 13q deletion; patient 2-TP53, 13q deletion & a subclone of trisomy 12; and patient 3-complext cytogenetics including 11q deletion.
At progression new somatic mutations observed: Patient 1-mutation in SF3B1 (K666T); Patients 2-increase in trisomy 12 subclone with associated MLL2 missence substitution, 8p deletion; and patient 3-8p deletion
At progression, however no mutations in BTK and BCR signaling pathway noted.
Implications:
- Resistance to BTK inhibition by CLL not uniformly associated with mutations in BCR signaling pathway, instead new somatic mutations or changes noted in patients who progressed on Ibrutinib.
View the original abstract on the ASH website.
