Scientists Create Novel Model That Shows Progression From Normal Blood Cells to Leukemia
Mount Sinai researchers have created a novel model that shows the step-by-step progression from normal blood cells to leukemia and its precursor diseases, creating replicas of the stages of the disease to test the efficacy of therapeutic interventions at each stage, according to a study to be published in Cell Stem Cell.
This research marked the first time scientists have been able to transplant leukemia from humans to a test tube and then into mice for study, a landmark feat that will allow for valuable research to help find therapies for blood cancer patients in the future.
“The new model will empower investigation into the cellular and molecular events underlying the development of leukemia in ways that were not possible before,” said Eirini P. Papapetrou, MD, PhD, Associate Professor of Oncological Sciences, Medicine, Hematology, and Medical Oncology at the Icahn School of Medicine at Mount Sinai. “These findings provide a framework to aid investigation into disease mechanisms, drug responses, and the cellular and molecular events driving leukemia progression.”
Scientists used CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat), a new, cutting-edge genome editing technology, to convert blood cells from patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) to particular stem cells (called induced pluripotent stem cells) that can mimic all stages of disease progression, from a healthy state to pre-malignancy and finally full-blown leukemia. Though scientists believe that cancer develops through a step-by-step process by which a normal cell transforms to a fully malignant cell through intermediate stages, recreating the steps was challenging with previous tools.
Scientists were able to manipulate the leukemia in a test tube environment, both by genetically modifying the disease-ridden stem cells at certain stages to revert to a pre-cancerous state, and by altering them so they would either progress to a severe or mild form of MDS. The ability to manipulate the leukemia to regress or progress will allow future researchers to test therapies that may be most potent at a particular stage, thus saving or extending a patient’s life.
Memorial Sloan Kettering Cancer Center was a valuable collaborator in this research. The lab of Michael G. Kharas, PhD, performed some of the mouse transplantation experiments in the study.
“We are encouraged by the discovery that it was possible to generate potent engraftable leukemia derived from AML induced pluripotent stem cells,” said Dr. Kharas, the co-corresponding author. “This work shows that integrated patient cell reprogramming and cancer genetics is a powerful way to dissect cancer progression.”
The progression model created through this research could also be used to develop models for more complex cancers, including solid tumors, the researchers said.
The research was funded by grants from the National Institutes of Health from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases (R01HL121570 and R00DK087923); the Damon Runyon Cancer Research Foundation, the Edward P. Evans Foundation, the Ellison Medical Foundation, the Henry and Marilyn Taub Foundation, the Babich Family Foundation and Alex’s Lemonade Stand Foundation.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.