A natural compound shows promise in enhancing the treatment of a particularly aggressive form of leukemia. Forskolin, which is derived from plants, has the potential to significantly improve therapies for KMT2A-rearranged Acute Myeloid Leukemia (KMT2A-r AML). Researchers from the University of Surrey have found that this natural substance could be instrumental in improving patient outcomes in this challenging disease.
Published findings in the British Journal of Pharmacology reveal that forskolin not only hampers the growth of leukemia cells, but also boosts the effectiveness of chemotherapy drugs. The research team at Surrey discovered that forskolin activates Protein Phosphatase 2A (PP2A), which subsequently reduces the activity of several genes associated with cancer progression, namely MYC, HOXA9, and HOXA10.
One particularly striking revelation from the study is how forskolin enhances the sensitivity of KMT2A-r AML cells to daunorubicin, a commonly used chemotherapy agent. Remarkably, this increased sensitivity does not solely depend on the activation of PP2A. Instead, forskolin appears to disrupt the function of P-glycoprotein 1, a protein that many cancer cells utilize to expel chemotherapy drugs. By inhibiting P-glycoprotein 1, forskolin allows daunorubicin to accumulate within the leukemia cells, thereby strengthening the treatment's efficacy.
In the words of Dr. Maria Teresa Esposito, a Senior Lecturer in Biochemistry at the University of Surrey: "Our research has unveiled an exciting dual mechanism of action for forskolin. It not only demonstrates direct anti-leukemic properties but also serves as a potent enhancer of conventional chemotherapy. By combining forskolin with daunorubicin, we could formulate a more effective treatment strategy that may allow for reduced chemotherapy doses and lessen the severe side effects commonly associated with AML therapies."
Dr. Simon Ridley, the Director of Research and Advocacy at Leukemia UK, remarked: "We are dedicated to funding pioneering research and take pride in supporting Dr. Esposito’s investigations. Acute Myeloid Leukemia is one of the most aggressive and lethal forms of cancer, and this study not only advances our understanding of KMT2A-rearranged AML but also paves the way for more compassionate, efficient treatments. Research like this is vital to our mission of doubling the five-year survival rate for AML over the next decade."
This important work was made possible through funding from Leukaemia UK and involved a collaborative effort among scientists from the University of Surrey, University of Roehampton, Barts Cancer Institute at Queen Mary University of London, Great Ormond Street Institute of Child Health at UCL, and the Genomic Regulation center in Barcelona, Spain.
