A research team led by the Icahn School of Medicine at Mount Sinai has built the first cellular model to depict the evolution of acute myeloid leukemia (AML), from its early to late stages. By using gene editing technologies to alter genes that make cells malignant, the team was able to identify potential therapeutic targets for early disease stages, according to a news release.
The therapeutic targets could be applicable not just to AML but also to the blood cancer myelodysplastic syndrome and clonal hematopoiesis, which is often a preleukemic condition.
AML is a cancer of the blood and bone marrow, the spongy tissue inside bones where blood cells are made. The disease, which primarily affects white blood cells, is one of the most common leukemias in adults, with more than 20,000 newly diagnosed cases each year in the United States.
While several new drugs have been introduced in recent years targeting the disease, they have fallen short of significantly changing patient outcomes or survival.
By introducing specific leukemia-causing gene mutations through CRISPR-mediated gene editing, Icahn Mount Sinai researchers were determined to better understand the successive stages of the evolution of leukemia. CRISPR is a powerful tool that allowed the team to alter the DNA sequences in induced pluripotent stem cells (iPSCs) to create a model with an increasing number of mutated genes that shows progressive malignant features that correspond to their human counterparts in myeloid disease.
CRISPR gene editing uses Cas9, an enzyme that acts like a pair of molecular scissors with the ability to cut strands of DNA. Through use of these tools, the researchers were able to recapitulate the step-by-step conversion of a normal cell into a malignant one.
Specifically, the researchers found that inflammatory and innate immunity pathways constitute such early targets and demonstrated that inhibitors of these pathways, therapies that are being trialed in blood cancers and immune-related disorders, may be promising therapeutic modalities for AML and myelodysplastic syndrome.
