醫學遺傳學及基因體學每月研討會 ─An Integrative Translational Study of Acute Myeloid Leukemia
周文堅 教授 (臺大醫院檢驗醫學部及內科部主治醫師)
Leukemia is a special topic of study. The discovery of Philadelphia chromosome in chronic myeloid leukemia (CML) in 1960s established a concept that cancers are genetic diseases. The introduction of imatinib for treatment of CML around year 2000 opened the era of target therapy. Through the contributions of scientists, our understanding of leukemia as well as the policies of treatment has dramatically changed. Acute myeloid leukemia (AML) is an aggressive disease with the highest annual incidence among leukemia in Taiwan. The prognosis has significantly improved, largely because of personalized treatment through fine stratification of the patients’ risk. We have been devoted to the translational study in AML in the past 10 years, thanks to the relative easy collection of tumor cells. The theme of our study is starting from sample archival; we collected decades of serial patients’ samples for genetic studies, including chromosomal analysis and mutation identification, by which we obtained a general clinical and genetic demographic picture and identified genetic markers for prognostication. We then proceeded to global mRNA and microRNA expression profiling, whereby we were able to identify expression signatures of prognostic significance and novel genetic markers critical to patients’ response to treatment. These efforts have further contributed to better selection of optimal treatment regimens for individual patients. In addition, the novel markers led us to explore their roles in prognosis and pathogenesis. We have also established a platform of animal modelling of AML, through which we could test the biological functions via in vivo experiments. In summary, our research platform is an integrative, bedside to bench approach, in which we get insights and generate hypotheses from clinical information and proceed to a mechanistic exploration through in vitro and in vivo animal studies.