[Biomarker for Hematopoietic Tumors--Aiming for Personalized Diagnosis of Leukemia Stem Cells]

Biomarkers are defined as characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Biomarkers obtained by PCR or flow cytometry are used for the diagnosis and subtyping of hematopoietic tumor cases. They are also used to predict the effectiveness of molecular-targeted therapies and detect minimal residual leukemia cells. In order to cure leukemia, it is necessary to eradicate leukemia stem cells. For that purpose, biomarkers to identify and characterize the leukemia stem cells in each case are needed. Therefore, we examined molecules involved in various stemness-related signaling pathways, especially NOTCH signaling in acute leukemia cells. In T-lymphoblastic leukemia cells, which often have activating NOTCH1 mutations, NOTCH works in oncogenic signaling. Although acute myeloid leukemia (AML) cells express NOTCH and NOTCH ligands, it is still controversial whether NOTCH is oncogenic or tumor-suppressive. To utilize the expression and activation of NOTCH as a leukemia stem cell biomarker, further investigation is required. Other stemness-related signaling molecules such as WNT, HEDGEHOG, HIF, and mTOR are also under investigation to assess whether they can be used as stem cell biomarkers in a clinical setting.