Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships
University of British Columbia
$81,667.00
Identification and Characterization of New MicroRNA Biomarkers in Chronic Myeloid Leukemia Stem Cells: Clinical Applications and Pathogenic Significance
EF 2011-12
Résumé
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.
Programme
Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships
Bénéficiaire
Emplacement
British Columbia, Canada
Type de bénéficiaire
Academia
Type
Grant
Source
CIHR Funding Decisions Database
Tel que publié
Id
257488
Name
Lin Hanyang
Region
British Columbia
Country
Canada
Orgtype
Research Institution; Institution Paid
Instname2
Cancer Research
Theme2
Biomedical
Prcname2
Doctoral Research Awards - A
Projecttitle
Identification and Characterization of New MicroRNA Biomarkers in Chronic Myeloid Leukemia Stem Cells: Clinical Applications and Pathogenic Significance
Programtype2
Studentship Programs
Orgnameinp2
University of British Columbia
Cihramount2
$81,667
Cihrequipment2
$0
Programname2
Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships
Keyworddelim
Cancer Stem Cell; Chronic Myeloid Leukemia; Colony Forming Cell Assay; Engraftment In Mice; Fluorescence-Activated Cell Sorting; Hematopoietic Stem Cells; Microrna; Progenitor Cell Assay; Retroviral Transduction; Stem Cell Assay
Abstract
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.
Competitiondate
201110
Approvedterm2
2 yrs 4 mths
Pinamesdelim
Lin, Hanyang
Approvedterm
2 ans 4 mois
Cihrcontribution2
~ $81,667~ $0~
