Study Title: Acquired multi-drug resistance in AML is caused by low apoptotic priming in relapsed myeloblasts
Publication: Blood Cancer Discovery
Dana-Farber Cancer Institute authors: Elyse A. Olesinski; Anthony Letai, MD, PhD; and Jacqueline Garcia, MD
Summary:
A cellular profiling method called dynamic BH3 profiling (DBP), developed by investigators at Dana-Farber Cancer Institute, has the potential to help guide personalized treatment for relapsed, drug-resistant acute myeloid leukemia (AML), according to a new study. Using patient-derived xenograft models of AML in mice, Dana-Farber investigators, in collaboration with Shruti Bhatt, PhD, and researchers at the National University in Singapore, found that a reduction in the signaling involved in programmed cell death - called mitochondrial apoptotic priming - plays a role in drug resistance alongside other factors, such as acquired genetic mutations. The team treated the models with a panel of targeted medicines for AML and profiled the treated cells using DBP. The test assesses the signaling associated with cell death and provides an indicator of a drug's potential to overcome resistance. The method predicted a response to drugs in animal models of AML and in human patients.
Significance:
Patients with relapsed AML have few treatment options because the disease often resists a broad range of medicines. This study shows that a cellular profiling method called DBP could provide a rapid and personalized mechanism for selecting potentially active medicines for patients. This possibility is being explored in a phase 2 prospective clinical trial at Dana-Farber that will use DBP to select therapies for patients with relapsed AML.
Funding:
Dana-Farber Cancer Institute, American Society of Hematology, National Medical Research Center of Singapore, Leukemia and Lymphoma Society, American Association of Cancer Research, EMBO (European Molecular Biology Organization), Ted and Eileen Pasquarello, National Institutes of Health, and the National Cancer Institute.
