Published: 2020-08-13 |
Source: National University of Singapore
Every year, 1.1 million new cases of blood cancers are diagnosed worldwide. Presently, chemotherapy remains the most common and effective course of treatment. However, the emergence of more aggressive forms of leukemia in adults prompts a need for early detection and new therapeutic approaches to achieve better clinical outcomes.
In a novel step forward. researchers from the Cancer Science Institute of Singapore (CSI) at the National University of Singapore (NUS) have identified covalently closed circular RNA's (circRNA's) from key genes involved in leukemia development and provided greater understanding of their roles in hematological malignancies.
Mutations in additional sex comb-like 1 (ASXL1) gene, an epigenetics remodeler, have been found in acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML) and myelodysplastic syndrome (MDS) and are associated with poor overall survival. Recently, the ASXL1 gene locus was shown to undergo alternative splicing to produce circRNA's. While previous studies on circRNA's in modulating the epigenetics landscape and the effects on differentiation in hematopoietic development and leukemogenesis. The findings of the study were published in the scientific journal Haematologica in July 2020.
Tapping on the newly established understanding, the research team aims to identify gene involved in myeloid differentiation program of hematopoietic stem cells (HSC's). These genes can in turn be targeted to restore the normal course of differentiation in leukemia or help induce apoptosis of immature and abnormally differentiated cells. The epigenetic signature identified could thus pave the way for future therapeutic developments of "epi-drugs."
Moving forward, the research team intends to generate data supporting the use of cicASXL1-1 in antisense therapy for malignant and non-malignant blood disorders using the newly acquired knowledge. More importantly, findings from this study will lay the foundation for the development of new RNA-based therapeutics for leukemia.