AKT-pathway inhibition in chronic lymphocytic leukemia reveals response relationships defined by TCL1.

Cell survival in chronic lymphocytic leukemia (CLL) largely depends on B-cell receptor-induced AKT activation. Gain-of-function genomic lesions of PI3K-AKT-mTOR pathway components are usually absent in CLL. We previously established that a BCR-mediated growth response in CLL is determined by the oncogene T-cell leukemia 1 (TCL1) through a sensitizer effect on AKT phospho-activation.

Pharmacologic interception in T-cell leukemia 1A associated pathways as a treatment rationale for chronic lymphocytic leukemia.

Recent therapeutic advances in chronic lymphocytic leukemia (CLL) are reflected by high response rates in most subsets of patients. However, refractory disease remains a problem, and virtually all of even the most sensitive tumors eventually recur. Therefore, ongoing efforts aim at the development of optimized interventional designs that more specifically target the strong pro-survival signature of the transformed B cell.