investigator_user investigator user funding collaborators pending menu bell message arrow_up arrow_down filter layers globe marker add arrow close download edit facebook info linkedin minus plus save share search sort twitter remove user-plus user-minus
  • Project leads
  • Collaborators

Identification of new microRNA biomarkers and candidate target genes in primitive CML cells using global comparative RNA analyses

Hanyang Lin

0 Collaborator(s)

Funding source

Canadian Institutes of Health Research (CIHR)
Chronic myeloid leukemia (CML) is a form of blood cancer, characterized by increased growth of white blood cells in the bone marrow and the accumulation of these cells in the blood. Its annual incidence is 1-2 per 100,000 people, and represents about 15-20% of all cases of adult leukemia in Western populations. CML displays a distinct mutation, the fusion of BCR-ABL gene, which causes ABL gene to be overly active. The recent introduction of imatinib mesylate (IM) medication has improved the treatment of CML by inhibiting ABL activity, but early relapses and the emergence of IM-resistant disease are an increasing problem. Currently, there are no effective molecular tests to predict patients' response to IM therapy. Also, growing evidence indicates that IM is not effective in eliminating leukemic stem cells, with disease returning after a period of apparent effect. Therefore, there is an urgent need to develop novel therapeutic strategies for treatment of CML. MicroRNAs (miRNAs) are small molecules that are able to regulate gene expression and have been found highly deregulated in many tumors, such as breast and prostate cancers. Previously, we have created miRNA expression profile comparing CML stem cells with normal blood stem cells, and found 30 abnormally expressed miRNAs. In this project I propose to identify and characterize miRNA biomarkers in CML stem cells. I will first validate these 30 miRNA expression in patient samples from IM-responders vs. IM-nonresponders to identify most significantly changed miRNAs. I will then compare patient samples before and after three-month treatment of nilotinib, a new ABL inhibitor that has recently approved as first-line therapy. This would allow identification of new biomarkers to predict patients' response to nilotinib for clinical use. In addition, I will characterize the roles of these miRNA biomarkers in CML stem cells, which could lead to development of novel therapies specifically targeting CML stem cells.

Related projects