Elucidating the mechanism of onset in chronic myeloproliferative neoplasms

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07/29/23

Introduction of Research by Division of Hygienic Chemistry, Faculty of Pharmacy, Keio University
Professor Megumi Tago

Professor Megumi Tago of the Division of Hygienic Chemistry, Faculty of Pharmacy, Keio University is focused on cancer and lifestyle-related diseases, and has been conducting research to elucidate the mechanism of onset in these diseases to find ways to prevent them. This laboratory is particularly focused on elucidating the mechanism of onset in chronic myeloproliferative neoplasm, a hematological cancer that very little is known about.

“My current focus is a type of hematological cancer called chronic myeloproliferative neoplasm. These are diseases in which abnormal increases in various hematological cells such as platelets and red blood cells occur, the cause of which remains unknown. In 2005, the causative gene was discovered. We made the causative gene ourselves by inducing mutation of the causative gene tyrosine kinase JAK2, and through genetic recombination, we actually introduced this gene into a cell. Applying biochemical techniques, we used the Western blotting or DNA electrophoresis to conduct research allowing us to determine what sort of signals the causative gene is sending from within these cells.”

In 2005, it was reported that a patient with chronic myeloproliferative neoplasm showed a point mutation (V617F) of tyrosine kinase JAK2 which is an important signal transmission gene for cytokines. Associate Professor Tago created the JAK2 point mutation (V617F) and has proven mutated JAK2 is a cancer gene that expresses potent transformative potential. Currently, she is focused on the gene group whose expression is induced downstream from the mutated JAK2, and by analyzing the function of these genes, hopes to elucidate the entirety of the signal transduction mechanism, and to further understanding of the mechanism of onset in Myeloproliferative Neoplasms.

“The body contains substances called cytokines, and various forms of these cytokines will be produced depending on each situation. The body’s homeostasis is maintained through production or reduction of these cytokines. After these cytokines elicit an effect, the tyrosine kinase, JAK2, plays an extremely important role in relaying information to cells. We are focusing on this genetic mutation that was actually discovered in a patient, to elucidate how this mutation might be related to disease, and how the abnormal protein JAK2 may activate downstream molecules.”

In recent years, newly-developed anticancer drugs target the molecules involved in cancer cell proliferation, infiltration, and metastases. As a result, molecularly-targeted drugs that inhibit these molecules are now becoming mainstream. Molecularly-targeted drugs can avoid damaging normal cells and will just attack malignant cells. This allows for improved treatment efficacy and fewer side effects from anticancer treatment.

“The phenomenon that actually occurs within the cell is not something that can easily be expressed in a model figure. Downstream from a single transcription factor is information on the expression of several hundred to several thousand genes. A thorough and multifaceted understanding of these phenomena will allow us to finally understand the disease and we try to examine diseases from various perspectives. Not only do we analyze the mechanism of cancer onset, but while most are derived from naturally-occurring medicinal plants, we also look at new compounds to see if they have any anticancer efficacy, hoping to these may provide potential new treatments.”