Annual Report 2019

Team Yokoyama

Akihiko Yokoyama, Hiroshi Okuda, Ryo Miyamoto, Satoshi Takahashi, Ayako Yokoyama

Introduction

We focus on molecular pathology of childhood cancers such as leukemia.

The Team and What We Do

 Our team investigate the molecular mechanisms of leukemia using mouse disease models and epigenome analytical tools. We aim to elucidate the molecular mechanisms by which leukemic oncoproteins cause aberrant gene regulation and identify novel molecular targets for drug development.

Research activities

 Most cancer cells express the MYC gene to promote proliferation. However, forced expression of MYC alone is insufficient to cause leukemia in mouse models, suggesting that additional factors are required for oncogenesis. We identified novel collaborative factors for MYC-mediated leukemogenesis. Moreover, we discovered that MOZ oncoproteins cause leukemic transformation in a similar mechanism to MLL oncoproteins, suggesting that similar therapeutic strategies can be applied to these leukemias.

1. Tatsumi G, Kawahara M, Imai T, Nishihata-Asai A, Nishida A, Inatomi O, Yokoyama A, Kakuta Y, Kito K, Andoh A. Thiopurine-mediated impairment of hamtopoietic stem and leukemia cells in Nudt15R138C knock-in mice. Leukemia 34(3):882-894 (2020) DOI ;10.1038/s41375-019-0583-9

2. Paubelle E, Zylbersztejn F, Maciel TT, Carvalho C, Mupo A, Cheok M, Lieben L, Sujobert P, Decroocq J, Yokoyama A, Asnafi V, Macintyre E, Tamburini J, Bardet V, Castaigne S, Preudhomme C, Dombret H, Carmeliet G, Bouscary D, Ginzburg YZ, de Thé H, Benhamou M, Monteiro RC, Vassiliou GS, Hermine O, Moura IC Vitamin D receptor controls cell stemness in acute myeloid leukemia and in normal bone marrow. Cell Reports. 30(3):739-754. (2020) doi: 10.1016/j.celrep.2019.12.055.)

Education

 Training a graduate school student from Kyoto University.

Future prospects

 Our research increases understanding of the molecular mechanisms of leukemia. Along the way, we will identify novel therapeutic targets, which may lead to development of new molecularly targeted therapies.