Possible Mechanisms Of Resistance To The Novel BH3-Mimetic ABT-199
Thijssen R, Geest CR, FM de Rooij M, et al.
Key Points:
- Investigators aimed to define signals that determine sensitivity for ABT-199 and ABT-737
- CD40 and IL4 stimulation reduced sensitivity to ABT-737 and ABT-199
- Dasatinib (prevents CD40-mediated resistance) and Abl inhibitor imatinib can overcome resistance for BH3-mimetics
- Dasatinib and ibrutinib abolished BCR- and chemokine-controlled adhesion
- Investigators postulated that Abl and Btk function play two key pro-survival arms; chemoresistance and localization in protective environment.
Implications:
- Long-term ABT-199 in CLL may select resistant clones
- Resistance may be overcome by combination treatment with kinase inhibitors
View the original abstract on the ASH website.
