Understanding the clonal origin, evolution, and progression of myeloid malignancies
Koichi Takahashi
MDThe University of Texas MD Anderson Cancer Center
Project Term: July 1, 2022 - June 30, 2027
The overarching focus of my research is to understand the clonal origin, evolution, and progression of myeloid malignancies and biological and clinical factors that influence the process. We tackle this question by analyzing patient samples with integrated approach combining single-cell omics, evolutionary genetics, and computational analytics. The ultimate goal of our research is to develop clinical strategies for early detection, prevention, and treatments of myeloid malignancies.
Myeloid malignancies such as acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are often diagnosed abruptly without early signs or pre-cancer phases. Currently, there is no practical way to detect early or prevent the development of MDS or AML. This is partly due to the lack of our understanding of how and when normal blood cells turn into malignant leukemia cells. The overall theme of our research program is to understand the entire history of how normal blood cells acquire genetic abnormalities and become AML and MDS. The ultimate goal of our research is to develop strategies for early detection, prediction, and prevention of AML and MDS. We tackle this problem by studying samples collected from AML and MDS patients using state-of-the-art technology that enables the analysis of genetic abnormalities in individual leukemia cells (this is called single-cell genomics technology). By comparing genetic profiles among individual leukemia cells using computational software, we rebuild the lifetime history of leukemia development. Some of the previous accomplishments of our research program include 1) discovering that AML/MDS that develops after exposure to chemotherapy (called therapy-related AML/MDS) is caused by preferentially selecting and expanding small premalignant blood cells called clonal hematopoiesis, and 2) describing that AML develops by acquiring genetic mutations in parallel like a branching tree. The ongoing research extends the investigation into how and when normal blood cells acquire genetic abnormalities and become AML/MDS and what types of chemotherapy cause preferential selection of premalignant blood cells. We believe that the successful completion of our research will significantly advance our understanding of how AML/MDS develops from normal blood cells. Eventually, the knowledge gained from these studies will help build strategies to prevent leukemia development and improve patients' lives at risk of developing leukemia.