Molecular mechanisms of acquired resistance to targeted therapies in CLL and strategies to overcome it. (A) Simplified scheme illustrating signaling pathways downstream of the BCR. Molecular targets of currently approved targeted therapies in CLL are indicated in red. (B) Mechanisms of acquired resistance to targeted therapies in CLL. (C) Strategies to prevent resistance to targeted therapies in CLL. (D) Strategies to overcome resistance to targeted therapies in CLL.