Harnessing Cell Lines as a Molecular Model for Therapeutic Biomarker Discovery in Pediatric Acute Lymphoblastic Leukaemia
By Yock-Ping Chow (yockping@ppukm.ukm.edu.my)
Cancer genomics is a rapidly growing research area and has accelerated the discovery of a long list of putative druggable mutations which yet to be proven their reliability as predictive biomarkers of drug response. Cancer cell lines recapitulating the genetic variation observed in patients are resourceful preclinical models for dissecting disease mechanisms as well as for systematic drug screening studies. To date, only few pediatric ALL cell lines are commercially available and they are insufficient to reflect the molecular heterogeneity of the disease. Hence, development of a larger collection of clinically annotated and characterized ALL cell lines is desirable to facilitate the discovery and validation of predictive biomarkers of response to matched anti-cancer therapies. In line with this clinical interest, we initiated this project by growing leukaemic cells isolated from patients’ bone marrow mononuclear cells using an in vitro culture system. Once established, the cell lines will be subjected for morphology assessment, karyotyping, immunophenotyping, and short tandem repeat genotyping to confirm their validity compared to original patients’ material. Subsequently, RNA-sequencing will be performed to identify potentially druggable candidate genes which can be harnessed for hypothesis driven gene-drug interaction studies. The validity of the predictive biomarkers of drug response will be further evaluated using in vivo models. Now, nearly 10 leukemic samples have been successfully sustained in vitro and in-depth investigation of their molecular characteristics is on-going.
