Aggressive natural killer-cell leukemia mutational landscape and drug profiling highlight JAK-STAT signaling as therapeutic target

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Author	Dufva Olli Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, FIN-00290, Helsinki, Finland Kankainen Matti Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FIN-00014, Helsinki, Finland Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, FIN-00290, Helsinki, Finland Kelkka Tiina Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, FIN-00290, Helsinki, Finland Sekiguchi Nodoka Department of Comprehensive Cancer Therapy, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan Awad Shady Adnan Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, FIN-00290, Helsinki, Finland Eldfors Samuli Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FIN-00014, Helsinki, Finland Yadav Bhagwan Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, FIN-00290, Helsinki, Finland Kuusanmaki Heikki Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, FIN-00290, Helsinki, Finland Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FIN-00014, Helsinki, Finland Malani Disha Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FIN-00014, Helsinki, Finland Andersson Emma I. Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, FIN-00290, Helsinki, Finland Pietarinen Paavo Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, FIN-00290, Helsinki, Finland Saikko Leena Department of Pathology, HUSLAB and Haartman Institute, University of Helsinki and Helsinki University Hospital, FIN-00290, Helsinki, Finland Kovanen Panu E. Department of Pathology, HUSLAB and Haartman Institute, University of Helsinki and Helsinki University Hospital, FIN-00290, Helsinki, Finland Ojala Teija Pharmacology, Faculty of Medicine, University of Helsinki, FIN-00014, Helsinki, Finland Lee Dean A. Nationwide Children’s Hospital, Division of Hematology, Oncology, and BMT, Columbus, OH, 43205, USA Loughran Thomas P. Jr. Department of Medicine, University of Virginia, Charlottesville, VA, 22908-0334, USA Nakazawa Hideyuki Division of Hematology, Internal Medicine, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan SUZUMIYA, Junji SUZUKI, Ritsuro Ko Young Hyeh Department of Pathology, Samsung Medical Center, Seoul, 0635, South Korea Kim Won Seog Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, 0635, South Korea Chuang Shih-Sung Department of Pathology, Chi-Mei Medical Center, Tainan, 71004, Taiwan Aittokallio Tero Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FIN-00014, Helsinki, Finland Chan Wing C. Department of Pathology, City of Hope National Medical Center, Duarte, CA, 91010, USA Ohshima Koichi Department of Pathology, Kurume University School of Medicine, Kurume, 830-0011, Japan Ishida Fumihiro Department of Biomedical Laboratory Sciences, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan Mustjoki Satu Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, FIN-00290, Helsinki, Finland Department of Clinical Chemistry, University of Helsinki, FIN-00014, Helsinki, Finland
Journal Title	NATURE COMMUNICATIONS
Volume	9
ISSN	2041-1723
Published Date	2018-04-19
DOI	10.1038/s41467-018-03987-2
PubMed ID	29674644
Publisher	NATURE PUBLISHING GROUP
NII Type	Journal Article
OAI-PMH Set	Faculty of Medicine
Remark	We thank the staff of High Throughput Biomedicine (Laura Turunen, Maria Nurmi, Jani Saarela) and Sequencing Laboratory (Pekka Ellonen, Sari Hannula, Aino Palva, Pirkko Mattila) Units at the Institute of Molecular Medicine Finland (FIMM) and Judith Klievink and other personnel of Hematology Research Unit Helsinki for their excellent technical assistance. We thank Dr. I-Ming Chen for kindly providing the IMC-1 cell line and Dr. Norio Shimizu for originally providing the SNK-6 cell line. This work was supported by the European Research Council (M-IMM project), Academy of Finland (grant no. 292605 and 287224), Tekes - the Finnish Funding Agency for Innovation (Dnro 6113/31/2016), Finnish special governmental subsidy for health sciences, research and training, the Sigrid Juselius Foundation, the Instrumentarium Science foundation, the Cancer Society of Finland, and the Finnish Cancer Institute. W.C.C. receives support from the City of Hope Cancer Center Support Grant (P30CA33572) and Lymphoma SPORE developmental project grant (1 P50 CA 136411-01 01A1 PP-4). F.I. was supported by KAKEN 15K09471 from Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Leukemia Research Fund; Takeda Pharmaceutical (inst); Cyugai Pharmaceutical (inst); Kyowa Hakko-Kirin (inst) and Pfizer (inst). The authors would like to thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about.