［January 22］44th IRCMS Seminar

December 27 2018

We would like to inform you that the 44th IRCMS Seminar has been scheduled as below. We would be pleased to see many of you participating in the seminar.

Date       : January 22, 2019 (Tue)
Time　　  : 11:00 - 12:00
Venue    :1F Meeting Lounge　International Research Center　for Medical Sciences(IRCMS)
Speaker : Masayuki Iwasaki, Ph.D
                Lecturer
                Institute of Laboratory Animals
                Tokyo Women's Medical University

Abstract: 

　The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mediates the metabolic catabolism and inactivation of prostaglandins. As a negative regulator of prostaglandin levels 15-PGDH mitigates their homeostatic, pathologic and oncogenic actions, and its pharmacologic inhibition constitutes a promising approach to transiently increase prostaglandin levels for regenerative therapy in various diseases.  Here we report that 15-PGDH has an alternative function to promote oncogenesis in addition to its previously characterized tumor suppressor role.  It is expressed at high levels in leukemia stem cells (LSCs), and is essential for the induction and maintenance of leukemias driven by HOX gene mis-regulation including MLL-rearranged AML. 15-PGDH lacks inherent oncogenic activity but nevertheless is required to sustain differentiation arrest, cycling activity, survival, in vivo progression, and LSC self-renewal indicative of non-oncogene addiction mediated through a non-canonical molecular function that does not require its dehydrogenase activity. Thus, 15-PGDH has an alternative, previously unappreciated oncogenic function that is independent of its known enzymatic activity yet essential for acute leukemia pathogenesis.  Our findings suggest that 15-PGDH may be a potential therapeutic target for anti-LSC therapy and a specific biomarker for LSCs in MLL-rearranged AML.