Nuclear export signal within CALM is necessary for CALM‐AF10‐induced leukemia

Cancer Science

Mai Suzuki¹  Kazutsune Yamagata¹  Mika Shino¹  Yukiko Aikawa¹  Koichi Akashi²  Toshio Watanabe³ 

[1] Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan;Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan;Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan

关键词: AF10;    chromosome translocation;    histone modification;    leukemia;    nuclear export signal;   

DOI  :  10.1111/cas.12347

来源: Wiley

【 摘 要 】

Abstract

The CALM–AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies. Certain HOXA cluster genes and MEIS1 genes are upregulated in patients and mouse models that express CALM-AF10. Wild-type clathrin assembly lymphoid myeloid leukemia protein (CALM) primarily localizes in a diffuse pattern within the cytoplasm, whereas AF10 localizes in the nucleus; however, it is not clear where CALM-AF10 acts to induce leukemia. To investigate the influence of localization on leukemogenesis involving CALM-AF10, we determined the nuclear export signal (NES) within CALM that is necessary and sufficient for cytoplasmic localization of CALM-AF10. Mutations in the NES eliminated the capacity of CALM-AF10 to immortalize murine bone-marrow cells in vitro and to promote development of acute myeloid leukemia in mouse models. Furthermore, a fusion of AF10 with the minimal NES can immortalize bone-marrow cells and induce leukemia in mice. These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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