Abstract:

Leukemia is a malignancy of serious harm to human health and its pathogenesis needs to be further clarified. With the rapid development of science and technology, study on disease mechanism is no longer limited to a single point of view, but aim to integrate the different levels of information, focus on mutual relations and interactions between molecules, in order to understand the systems biological dysfunction in the disease. Thus, using systems biological methods to study in depth the leukemia development, and in this setting, applying the idea of translational medicine to explore the targeted therapy of leukemia, has an important significance for the final capture of the disease. During the construction of the “211 Project”, Shanghai Institute of Hematology has made a major breakthrough in the basic and clinical studies of differentiation and apoptosis-induced targeted therapy of acute promyelocytic leukemia (APL), making APL the first curable acute myeloid leukemia, and the successful example of leukemia gene product-based targeted therapy. This will be further extended to other types of leukemia. Also, our group has made a significant progress on leukemia systems biology research, being the first to carry out the Leukemia Genome Anatomy Project. Using exome sequencing of acute monocytic leukemia, we identify the mutations and epigenetic changes of DNA methyltransferase 3A (DNMT3A) gene, which is closely related to the clinical diagnosis and prognosis of leukemia patients. We also study at the genome-wide level the APL pathogenesis and illustrate the target genes transcriptionally repressed by PML-RARα oncoprotein. These results not only provide guidance on leukemia pathogenesis, molecular typing and standardized clinical pathway of leukemia, but also deepen the theoretical connotations of “translational medical research” and use target therapy to save thousands of leukemia patients world-wide.

Key words: leukemia, system biology, targeted therapy