Development of Leukemia Based Precision Medicine Research Model on Non-Invasive Apoptosis Detection Platform – Application of Crispr/Cas9 Gene and Target Therapy on Philadelphia Chromosome of Chronic Myelogenous Leukemia as an Example

In Taiwan, the diagnosis of leukemia patients is about 1100 cases per year. Among all different kinds of leukemia, Chromic Myeloid Leukemia (CML) is the most common disease in adults, also found DNA translocation of BCR-ABL oncogene (Philadelphia chromosome, Ph). Currently, the treatments for CML include radiation therapy, tyrosine kinase inhibitors (TKI) and hematopoietic stem cell transplantation. However, TKI treatment is a time consuming and expensive therapy, also it causes serious side effects in clinic. Thus, the development of novel therapeutic for personalized medicine is despairing needed. The current methodology of apoptosis detection includes cell morphology observation, DNA degradation analysis, TdT mediated dUTP nick end labeling (TUNEL) and flow cytometry measurement. The above platforms require massive labor, time consuming man power and a lot of tissue cells as research material. Therefore, it is difficult to define the appropriate customized anti-cancer drugs or therapeutic strategy on clinical surgery samples. Our research team has completed the following models: 1. Build a Non-Invasive Apoptosis Detection Sensor (NIDAS) platform. Through these research platforms. 2. Identify the key molecule by TCGA (The Cancer Genome Atlas, TCGA) database analysis. 3. CRISPR/CAS9 gene editing technics. Through these research platforms, we have initially established personalized leukemia medicine platform. We aim to complete 10 cases of personalized leukemia medication through using PDC (Patient-derived cells) or PDX (Patient-derived xenograft) models. Our research team includes clinical medicine, bioinformatics, basic study and animal investigations, aim to develop a personalized medicine on ex-vivo tumor tissues, providing effective anti-cancer therapy. Our one-year proposal will be completed in accordance to the following aims:Aim: Using NIADS and patient-derived cells (PDC) or Patient-derived xenograft (PDX) to establish a personalized medicine and evaluating clinical leukemia efficacy.1-1 Developing second generation of NIADS and optimizing virus infection efficiency.1-2 Standardizing the protocols of leukemia PDC cell culture and establishing anti-cancer drug combo.1-3 Establishing PDX model on humanized mice.1-4 Evaluating the prognosis of personalized medicine model.