Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia

Summary

• ・A novel EVI1 splice isoform is frequently expressed in poor-prognostic leukemia harboring inv(3)/t(3;3) and drives myeloid transformation.
• ・Frequent SF3B1 mutations in inv(3)/t(3;3) leukemia generate a novel EVI1 isoform with an altered second Zinc finger DNA-binding domain.
• ・These results explain the reason why splicing factor SF3B1 mutation is very frequently mutated in inv(3)/t(3;3) leukemia

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１ Research Paper

Authors:
Atsushi Tanaka^1,2, Taizo A. Nakano³, Masaki Nomura^1,4, Hiromi Yamazaki¹, Jan P. Bewersdorf⁵, Roger Mulet-Lazaro^6,7, Simon Hogg⁵, Bo Liu⁵, Alex Penson⁵, Akihiko Yokoyama⁸, Weijia Zang^1,9, Marije Havermans^6,7, Miho Koizumi¹⁰, Yasutaka Hayashi¹, Hana Cho⁵, Akinori Kanai^11,12, Stanley C. Lee^13,14, Muran Xiao^1,15, Yui Koike¹, Yifan Zhang^1,9, Miki Fukumoto¹, Yumi Aoyama^1,9, Tsuyoshi Konuma¹⁶, Hiroyoshi Kunimoto¹⁷, Toshiya Inaba¹¹, Hideaki Nakajima¹⁷, Hiroaki Honda¹⁰, Hiroshi Kawamoto², Ruud Delwel^6,7, Omar Abdel-Wahab^5,*, Daichi Inoue^1,*

Affiliations:

• ¹Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
• ²Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
• ³Department of Pediatrics, Section of Hematology, Oncology and Bone Marrow Transplantation, University of Colorado, Aurora, CO, United States.
• ⁴Facility for iPS Cell Therapy, CiRA Foundation, Kyoto, Japan.
• ⁵Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
• ⁶Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
• ⁷Oncode Institute, Utrecht, the Netherlands.
• ⁸Tsuruoka Metabolomics Laboratory, National Cancer Center, Yamagata, Japan.
• ⁹Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
• ¹⁰Field of Human Disease Models, Major in Advanced Life Sciences and Medicine, Tokyo Women’s Medical University, Tokyo, Japan.
• ¹¹Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
• ¹²Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
• ¹³Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
• ¹⁴Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
• ¹⁵Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
• ¹⁶Structural Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa, Japan.
• ¹⁷Department of Stem Cell and Immune Regulation, Graduate School of Medicine, Yokohama City University, Yokohama, Kanagawa, Japan.

Title of original: Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia
Journal: Blood
doi: 10.1182/blood.2021015325.

Authors

Atushi Tanaka

Daichi Inoue