Abstract
AbstractJones et al address a critical issue in the field of FMS-like tyrosine kinase 3/internal tandem duplication–positive (FLT3/ITD+) leukemias, the fact that FLT3 inhibitors demonstrate superior activity against peripheral compared to bone marrow disease. They demonstrate that expression of cytochrome P450 enzymes (CYPs), in particular CYP3A4, play a major role in bone marrow stromal cell–mediated inhibition in the activity of several FLT3 inhibitors. Their findings suggest combining CYP inhibitors with FLT3 inhibitors may enhance clearance of bone marrow disease. These findings may have major implications for the treatment of FLT3+ acute myeloid leukemia.
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