Researchers have developed a mouse model to help them understand why patients with RUNX1-mutated acute myeloid leukemia (AML) respond poorly to chemotherapy.
Approximately 15% of AML patients harbor a mutation in the RUNX1 gene.
In these patients, anthracycline/cytarabine-based chemotherapy does not eradicate AML cells from the bone marrow.
But scientists don’t fully understand the underlying mechanisms protecting these residual cells.
Jason H. Mendler, MD, PhD, of the University of Rochester Medical Center in Rochester, New York, and his colleagues have suggested that a genetically defined mouse model of RUNX1-mutated AML is the ideal platform to investigate the cellular mechanisms protecting residual AML cells in this disease subtype.
“Like all cancers, leukemia is not a one-size-fits-all, and, therefore, it’s important to find better ways to study high-risk subtypes of the disease,” Dr Mendler said. “We believe our mouse model will allow us to quickly define new ways to target this challenging disease.”
Dr Mendler and his colleagues described their model in PLOS ONE.
The researchers began with a patient-derived cell line of RUNX1-mutated, cytogenetically normal AML. They injected these cells into NOD-SCID-γ mice and observed leukemic engraftment in the bone marrow, spleen, and peripheral blood within 6 weeks.
When the researchers treated the mice with anthracycline/cytarabine-based chemotherapy, they saw AML clearance in the spleen and peripheral blood. But leukemic cells remained in the bone marrow.
Dr Mendler and his colleagues also found their mouse model contained mutations in 5 genes aside from RUNX1—ASXL1, CEBPA, GATA2, NRAS, and SETBP1.
The team said further investigation will be focused on identifying the interplay of genes and pathways that are critical to mediating chemotherapy resistance in this model.
