Predicting response to alvocidib by mitochondrial profiling
View Patent ↗The present disclosure provides diagnostic methods useful for predicting a patient's response to alvocidib and guiding a physician decision to administer alvocidib to the patient.
1. A method of treating a mammal with acute myeloid leukemia (AML) whose disease is dependent on MCL-1 comprising administering alvocidib, cytarabine, and mitoxantrone to the mammal with bone marrow cells having MCL-1 priming of at least 40% determined by subjecting cells from the mammal's bone marrow to a BH3 mimetic that is selective for MCL-1 and determining the percentage change in the mitochondrial polarization which corresponds to the MCL-1 priming.
2. The method of claim 1 wherein the determination of MCL-1 priming includes permeabilizing the bone marrow cells.
3. The method of claim 1 wherein the AML is refractory.
4. The method of claim 1 wherein the AML is relapsed or refractory.
5. A method of treating a mammal with acute myeloid leukemia (AML) whose disease is dependent on MCL-1 comprising:
acquiring a plurality of bone marrow cells from the mammal;
determining an MCL-1 priming of the bone marrow cells determined by subjecting cells from the mammal's bone marrow to a BH3 mimetic that is selective for MCL-1 and determining the percentage change in the mitochondrial depolarization which corresponds to the MCL-I priming; and
administering alvocidib, cytarabine, and mitoxantrone to the mammal if the bone marrow cells have the MCL-1 priming of at least 40%.
6. The method of claim 5 wherein the determination of MCL-1 priming includes permeabilizing the bone marrow cells.
7. The method of claim 5 wherein the AML is refractory.
8. The method of claim 5 wherein the AML is relapsed or refractory.