The Pathogenetic Significance of Deregulated Transcription Factors in Hematological Malignancies
Hematological malignancies have been treated with traditional chemotherapy, such as alkylating agents, anthracycline, or antimetabolites. These conventional chemotherapies are not specific to malignant cells, and severe side effects are unavoidable with intensive chemotherapy. Therefore, it might be difficult to improve the cure rate further with conventional chemotherapy. Hematopoietic stem cell transplantation (HSCT) is a powerful and curable treatment, but it is very invasive. Patients sometimes suffer from severe side effects, such as graft-versus-host disease (GVHD), and HSCT may also cause premature death. In addition, it is sometimes difficult to find appropriate donors. In recent years, with the great advances in molecular biology, genetics, biochemistry, and systems biology, we gradually come to understand the molecular mechanisms of pathogenesis in hematological malignancies. Molecular targeted therapy targets molecules or pathways that play critical roles in maintaining hematological malignancies. In contrast to conventional chemotherapy, molecular targeted therapy is highly specific to malignant cells and has minimal side effects. Currently, the most successful molecular targeted therapy is imatinib, a relatively specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia (CML). Imatinib dramatically changed the standard therapy and indication of HSCT for CML [1,2]. However, in contrast to CML, which is relatively homogeneous, molecular pathogenesis and therapeutic targets are largely unknown in many hematological malignancies. Therefore, we definitely need to elucidate molecular mechanisms of pathogenesis in other types of hematopoietic malignancies. Classically, we analyzed the functions of molecules individually, which method was not necessarily efficient. To extensively clarify molecular pathogenesis in many hematological malignancies, we applied bioinfor-matics and systems biology. We made genome-wide analyses of intracellular changes caused by leukemia-associated transcriptional factors, with the intention to comprehend total molecular pathogenesis and to identify therapeutic targets.
KeywordsAcute Myeloid Leukemia Chronic Myeloid Leukemia Hematopoietic Stem Cell Transplantation Hematological Malignancy Acute Myeloid Leukemia Patient
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