SINGAPORE A research team led by the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore has identified ways to inhibit the function of a key protein linked to stem cell-like behavior in terminal-stage chronic myeloid leukemia (CML), making it possible to develop drugs that may extend the survival of these patients.
The study, published in the prestigious international journal Proceedings of the National Academy of Sciences, is the result of a long-standing collaboration between Duke-NUS, the Experimental Therapeutics Centre at the Agency for Science, Technology and Research (A*STAR), and the Singapore General Hospital that is focused on developing effective therapies in CML.
CML is a blood cancer that has seen tremendous improvement in treatment outcomes following the introduction of tyrosine kinase inhibitor (TKI) drugs that specifically target the BCR-ABL fusion gene, a genetic abnormality that is characteristic of CML. However, when CML progresses to its terminal stage, known as the blast crisis phase, TKI drugs become ineffective and patients with blast crisis CML rapidly succumb to the disease.
"TKI therapy is highly effective in chronic phase CML, and enables most patients to survive many years. In contrast, patients with blast crisis CML usually succumb to their disease within one year, with most patients dying because they develop drug resistance to TKI therapy," said principal investigator Ong Sin Tiong, associate professor and head of the Laboratory of Hematologic Malignancies in the Cancer and Stem Cell Biology Program at Duke-NUS.
A subset of cells associated with blast crisis CML exhibit characteristics of self-renewing stem cells, suggesting that targeting this particularly malignant and drug-resistant population would be effective in treating blast crisis CML. The team therefore searched for novel targets that will specifically eliminate these cancer stem cells.
Through their efforts, the
|Contact: Juliana Chan|
Duke University Medical Center