Tejal Somvanshi
Scientists at the University of Birmingham have developed a powerful new breakthrough lab model that could speed up the search for treatments for an aggressive blood cancer, according to research published in Nature Communications.
The team focused on myelodysplastic syndrome (MDS), a blood cancer that affects about 4 in 100,000 people each year. MDS often progresses to acute myeloid leukemia (AML), a far more dangerous condition with poor survival rates.
In this groundbreaking study, researchers created a “true-to-life” model using induced pluripotent stem cells from actual MDS patients. These special cells can be reprogrammed to develop into different cell types, allowing scientists to observe disease progression in a controlled environment.
“Our study using blood cancer cells from a patient with MDS before and after disease progression presents two exciting developments,” said Dr. Paloma Garcia, lead author of the study from the University of Birmingham. “Firstly, we developed a powerful and true to life model for future research using induced pluripotent stem cells from an actual patient. Secondly, the confirmation that the mutation of the CEBPA gene plays such an important role in disease progression presents a significant step towards new ways to treat and diagnose MDS.”
The research team specifically examined whether changes to the CEBPA gene were driving disease progression in MDS patients. They took blood cells from a patient diagnosed with MDS and reprogrammed them into iPSCs. These cells were then converted into white and red blood cells in the lab.
By modifying the cells’ genome to include the CEBPA mutation that occurred in the patient two years after diagnosis, they observed the same changes that happened in the actual patient – reduced healthy cells, blocked formation of white blood cells, and rapidly dividing abnormal cells that resisted chemotherapy.
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Professor Constanze Bonifer, a Birmingham Emeritus Professor and senior author on the paper, explained: “The experiments revealed that adding the CEBPA mutation to the mix of mutations that were already there alters how DNA is organised in blood cells, which completely changed gene activity and pushed the cells on the path to malignancy.”
The finding is particularly significant because MDS that progresses to AML has a poor prognosis. Studies show that patients who transform to AML have a significantly higher risk of death, with median overall survival dropping to about 15 months compared to 31 months for those who don’t transform.
Current treatments for MDS include supportive care, hypomethylating agents like azacitidine and decitabine, and stem cell transplants for eligible patients. However, the transformation to AML often makes the disease more resistant to therapy.
Dr. Garcia believes this new model could form the basis for comprehensive drug screening experiments to find effective treatments for what is currently a highly aggressive blood cancer with limited options.
The research team is open to collaboration, licensing, or partnering opportunities to further develop this promising approach in the fight against blood cancer.
