Mechanisms of resistance to targeted therapies in acute myeloid leukemia and chronic myeloid leukemia.
Small molecule kinase inhibitors of BCR-ABL in chronic myeloid leukemia (CML) and of FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in acute myeloid leukemia (AML) have been successful at achieving remissions in these diseases as monotherapy, but these leukemias do not initially respond in a subset of patients (primary resistance) and they progress in an additional group of patients after an initial response (secondary resistance). Resistance to these agents can be divided into mechanisms that allow reactivation kinase activity and those that bypass reliance on oncogenic signaling mediated by the target kinase. Elucidation of clinical resistance mechanisms to targeted therapies for patients can provide important insights into disease pathogenesis and signaling.
From the Division of Hematology/Oncology, University of California, San Francisco, CA.
Catherine C
CC
Smith
From the Division of Hematology/Oncology, University of California, San Francisco, CA.
Neil P
NP
Shah