Novel etiology of autoimmune disorders: the role of acquired somatic mutations in lymphoid cells

Project Information

M-Imm

Grant agreement ID: 647355

DOI 10.3030/647355

Project closed

EC signature date 28 August 2015

Start date 1 September 2015

End date 28 February 2021

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost € 2 047 337,00

EU contribution € 2 047 337,00

Coordinated by

HELSINGIN YLIOPISTO
Finland

Publications

Peer reviewed articles (24)

Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease

Author(s): Daehong Kim, Giljun Park, Jani Huuhtanen, Sofie Lundgren, Rajiv K. Khajuria, Ana M. Hurtado, Cecilia Muñoz-Calleja, Laura Cardeñoso, Valle Gómez-García de Soria, Tzu Hua Chen-Liang, Samuli Eldfors, Pekka Ellonen, Sari Hannula, Matti Kankainen, Oscar Bruck, Anna Kreutzman, Urpu Salmenniemi, Tapio Lönnberg, Andrés Jerez, Maija Itälä-Remes, Mikko Myllymäki, Mikko A. I. Keränen, Satu Mustjok
Published in: Nature Communications, Issue 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-16115-w

Adult-Onset Anti-Citrullinated Peptide Antibody-Negative Destructive Rheumatoid Arthritis Is Characterized by a Disease-Specific CD8+ T Lymphocyte Signature

Author(s): Tiina Kelkka, Paula Savola, Dipabarna Bhattacharya, Jani Huuhtanen, Tapio Lönnberg, Matti Kankainen, Kirsi Paalanen, Mikko Tyster, Maija Lepistö, Pekka Ellonen, Johannes Smolander, Samuli Eldfors, Bhagwan Yadav, Sofia Khan, Riitta Koivuniemi, Christopher Sjöwall, Laura L. Elo, Harri Lähdesmäki, Yuka Maeda, Hiroyashi Nishikawa, Marjatta Leirisalo-Repo, Tuulikki Sokka-Isler, Satu Mustjoki
Published in: Frontiers in Immunology, Issue 11, 2020, ISSN 1664-3224
Publisher: Frontiers Media SA
DOI: 10.3389/fimmu.2020.578848

Predicting recognition between T cell receptors and epitopes with TCRGP

Author(s): Emmi Jokinen, Jani Huuhtanen, Satu Mustjoki, Markus Heinonen, Harri Lähdesmäki
Published in: PLOS Computational Biology, Issue 17/3, 2021, Page(s) e1008814, ISSN 1553-7358
Publisher: Public Library of Science
DOI: 10.1371/journal.pcbi.1008814

Genomic landscape characterization of large granular lymphocyte leukemia with a systems genetics approach

Author(s): A Coppe, E I Andersson, A Binatti, V R Gasparini, S Bortoluzzi, M Clemente, M Herling, J Maciejewski, S Mustjoki, S Bortoluzzi
Published in: Leukemia, Issue 31/5, 2017, Page(s) 1243-1246, ISSN 0887-6924
Publisher: Nature Publishing Group
DOI: 10.1038/leu.2017.49

High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia

Author(s): E. I. Andersson, T. Tanahashi, N. Sekiguchi, V. R. Gasparini, S. Bortoluzzi, T. Kawakami, K. Matsuda, T. Mitsui, S. Eldfors, S. Bortoluzzi, A. Coppe, A. Binatti, S. Lagstro m, P. Ellonen, N. Fukushima, S. Nishina, N. Senoo, H. Sakai, H. Nakazawa, Y.-L. Kwong, T. P. Loughran, J. P. Maciejewski, S. Mustjoki, F. Ishida
Published in: Blood, Issue 128/20, 2016, Page(s) 2465-2468, ISSN 0006-4971
Publisher: American Society of Hematology
DOI: 10.1182/blood-2016-06-724856

Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis

Author(s): P. Savola, T. Kelkka, H. L. Rajala, A. Kuuliala, K. Kuuliala, S. Eldfors, P. Ellonen, S. Lagström, M. Lepistö, T. Hannunen, E. I. Andersson, R. K. Khajuria, T. Jaatinen, R. Koivuniemi, H. Repo, J. Saarela, K. Porkka, M. Leirisalo-Repo, S. Mustjoki
Published in: Nature Communications, Issue 8, 2017, Page(s) 15869, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/ncomms15869

A novel class of somatic mutations in blood detected preferentially in CD8 + cells

Author(s): Miko Valori, Lilja Jansson, Anna Kiviharju, Pekka Ellonen, Hanna Rajala, Shady Adnan Awad, Satu Mustjoki, Pentti J. Tienari
Published in: Clinical Immunology, Issue 175, 2017, Page(s) 75-81, ISSN 1521-6616
Publisher: Academic Press
DOI: 10.1016/j.clim.2016.11.018

Patient-customized Drug Combination Prediction and Testing for T-cell Prolymphocytic Leukemia Patients

Author(s): Liye He, Jing Tang, Emma I Andersson, Sanna Timonen, Steffen Koschmieder, Krister Wennerberg, Satu Mustjoki, Tero Aittokallio
Published in: Cancer Research, 2018, Page(s) canres.3644.2017, ISSN 0008-5472
Publisher: American Association for Cancer Research
DOI: 10.1158/0008-5472.CAN-17-3644

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling

Author(s): Heikki Kuusanmäki, Olli Dufva, Elina Parri, Arjan J. van Adrichem, Hanna Rajala, Muntasir M. Majumder, Bhagwan Yadav, Alun Parsons, Wing C. Chan, Krister Wennerberg, Satu Mustjoki, Caroline A. Heckman
Published in: Oncotarget, Issue 8/57, 2017, ISSN 1949-2553
Publisher: Impact Journals
DOI: 10.18632/oncotarget.22178

Divergent roles for antigenic drive in the aetiology of primary versus dasatinib-associated CD8+ TCR-Vβ+ expansions

Author(s): Anna Lissina, James E. McLaren, Mette Ilander, Emma I. Andersson, Catherine S. Lewis, Mathew Clement, Andrew Herman, Kristin Ladell, Sian Llewellyn-Lacey, Kelly L. Miners, Emma Gostick, J. Joseph Melenhorst, A. John Barrett, David A. Price, Satu Mustjoki, Linda Wooldridge
Published in: Scientific Reports, Issue 8/1, 2018, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-017-18062-x

Somatic STAT3 mutations in Felty syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia

Author(s): Paula Savola, Oscar Brück, Thomas Olson, Tiina Kelkka, Markku J. Kauppi, Panu E. Kovanen, Soili Kytölä, Tuulikki Sokka-Isler, Thomas P. Loughran, Marjatta Leirisalo-Repo, Satu Mustjoki
Published in: Haematologica, Issue 103/2, 2018, Page(s) 304-312, ISSN 0390-6078
Publisher: Ferrata Storti Foundation
DOI: 10.3324/haematol.2017.175729

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

Author(s): Olli Dufva, Matti Kankainen, Tiina Kelkka, Nodoka Sekiguchi, Shady Adnan Awad, Samuli Eldfors, Bhagwan Yadav, Heikki Kuusanmäki, Disha Malani, Emma I Andersson, Paavo Pietarinen, Leena Saikko, Panu E. Kovanen, Teija Ojala, Dean A. Lee, Thomas P. Loughran, Hideyuki Nakazawa, Junji Suzumiya, Ritsuro Suzuki, Young Hyeh Ko, Won Seog Kim, Shih-Sung Chuang, Tero Aittokallio, Wing C. Chan, Koichi Ohshim
Published in: Nature Communications, Issue 9/1, 2018, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-018-03987-2

ADA2 deficiency: Clonal lymphoproliferation in a subset of patients

Author(s): Luca Trotta, Timi Martelius, Timo Siitonen, Timo Hautala, Sari Hämäläinen, Hanna Juntti, Mervi Taskinen, Mette Ilander, Emma Irene Andersson, Andrey Zavialov, Meri Kaustio, Riikka Keski-Filppula, Michael Hershfield, Satu Mustjoki, Terhi Tapiainen, Mikko Seppänen, Janna Saarela
Published in: Journal of Allergy and Clinical Immunology, Issue 141/4, 2018, Page(s) 1534-1537.e8, ISSN 0091-6749
Publisher: Mosby Inc.
DOI: 10.1016/j.jaci.2018.01.012

Sex bias in MHC I-associated shaping of the adaptive immune system

Author(s): Tilman Schneider-Hohendorf, Dennis Görlich, Paula Savola, Tiina Kelkka, Satu Mustjoki, Catharina C. Gross, Geoffrey C. Owens, Luisa Klotz, Klaus Dornmair, Heinz Wiendl, Nicholas Schwab
Published in: Proceedings of the National Academy of Sciences, Issue 115/9, 2018, Page(s) 2168-2173, ISSN 0027-8424
Publisher: National Academy of Sciences
DOI: 10.1073/pnas.1716146115

Clonal hematopoiesis in patients with rheumatoid arthritis

Author(s): Paula Savola, Sofie Lundgren, Mikko A. I. Keränen, Henrikki Almusa, Pekka Ellonen, Marjatta Leirisalo-Repo, Tiina Kelkka, Satu Mustjoki
Published in: Blood Cancer Journal, Issue 8/8, 2018, ISSN 2044-5385
Publisher: Nature Publishing Group
DOI: 10.1038/s41408-018-0107-2

Phenotype-based drug screening reveals association between venetoclax response and differentiation stage in acute myeloid leukemia

Author(s): Heikki Kuusanmäki, Aino-Maija Leppä, Petri Pölönen, Mika Kontro, Olli Dufva, Debashish Deb, Bhagwan Yadav, Oscar Brück, Ashwini Kumar, Hele Everaus, Bjørn T. Gjertsen, Merja Heinäniemi, Kimmo Porkka, Satu Mustjoki, Caroline A. Heckman
Published in: Haematologica, Issue 105/3, 2020, Page(s) 708-720, ISSN 0390-6078
Publisher: Ferrata Storti Foundation
DOI: 10.3324/haematol.2018.214882

STAT3 Mutation Is Associated with STAT3 Activation in CD30+ ALK− ALCL

Author(s): Emma I. Andersson, Oscar Brück, Till Braun, Susanna Mannisto, Leena Saikko, Sonja Lagström, Pekka Ellonen, Sirpa Leppä, Marco Herling, Panu E. Kovanen, Satu Mustjoki
Published in: Cancers, Issue 12/3, 2020, Page(s) 702, ISSN 2072-6694
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cancers12030702

Subclonal STAT3 mutations solidify clonal dominance

Author(s): Cassandra M. Kerr, Michael J. Clemente, Peter W. Chomczynski, Bartlomiej Przychodzen, Yasunobu Nagata, Vera Adema, Valeria Visconte, Alan E. Lichtin, Satu Mustjoki, Tomas Radivoyevitch, Mikkael A. Sekeres, Jaroslaw P. Maciejewski
Published in: Blood Advances, Issue 3/6, 2019, Page(s) 917-921, ISSN 2473-9529
Publisher: American Society of Hematology
DOI: 10.1182/bloodadvances.2018027862

Twins with different personalities: STAT5B—but not STAT5A—has a key role in BCR/ABL-induced leukemia

Author(s): Sebastian Kollmann, Eva Grundschober, Barbara Maurer, Wolfgang Warsch, Reinhard Grausenburger, Leo Edlinger, Jani Huuhtanen, Sabine Lagger, Lothar Hennighausen, Peter Valent, Thomas Decker, Birgit Strobl, Mathias Mueller, Satu Mustjoki, Andrea Hoelbl-Kovacic, Veronika Sexl
Published in: Leukemia, Issue 33/7, 2019, Page(s) 1583-1597, ISSN 0887-6924
Publisher: Nature Publishing Group
DOI: 10.1038/s41375-018-0369-5

A robust pipeline with high replication rate for detection of somatic variants in the adaptive immune system as a source of common genetic variation in autoimmune disease

Author(s): Lies Van Horebeek, Kelly Hilven, Klara Mallants, Annemarie Van Nieuwenhuijze, Tiina Kelkka, Paula Savola, Satu Mustjoki, Susan M Schlenner, Adrian Liston, Bénédicte Dubois, An Goris
Published in: Human Molecular Genetics, Issue 28/8, 2018, Page(s) 1369-1380, ISSN 0964-6906
Publisher: Oxford University Press
DOI: 10.1093/hmg/ddy425

Somatic mutations and T-cell clonality in patients with immunodeficiency

Author(s): Paula Savola, Timi Martelius, Matti Kankainen, Jani Huuhtanen, Sofie Lundgren, Yrjö Koski, Samuli Eldfors, Tiina Kelkka, Mikko A.I. Keränen, Pekka Ellonen, Panu E. Kovanen, Soili Kytölä, Janna Saarela, Harri Lähdesmäki, Mikko R.J. Seppänen, Satu Mustjoki
Published in: Haematologica, 2020, Page(s) haematol.2019.220889, ISSN 0390-6078
Publisher: Ferrata Storti Foundation
DOI: 10.3324/haematol.2019.220889

A high definition picture of somatic mutations in chronic lymphoproliferative disorder of natural killer cells

Author(s): Vanessa Rebecca Gasparini, Andrea Binatti, Alessandro Coppe, Antonella Teramo, Cristina Vicenzetto, Giulia Calabretto, Gregorio Barilà, Annica Barizza, Edoardo Giussani, Monica Facco, Satu Mustjoki, Gianpietro Semenzato, Renato Zambello, Stefania Bortoluzzi
Published in: Blood Cancer Journal, Issue 10/4, 2020, ISSN 2044-5385
Publisher: Nature Publishing Group
DOI: 10.1038/s41408-020-0309-2

Reinstated p53 response and high anti-T-cell leukemia activity by the novel alkylating deacetylase inhibitor tinostamustine

Author(s): S. Pützer, L. Varghese, J. von Jan, T. Braun, A. K. Giri, P. Mayer, N. Riet, S. Timonen, S. Oberbeck, H. Kuusanmäki, S. Mustjoki, M.-H. Stern, T. Aittokallio, S. Newrzela, A. Schrader, M. Herling
Published in: Leukemia, 2020, ISSN 0887-6924
Publisher: Nature Publishing Group
DOI: 10.1038/s41375-020-0772-6

Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia

Author(s): Sofie Lundgren, Mikko A. I. Keränen, Matti Kankainen, Jani Huuhtanen, Gunilla Walldin, Cassandra M. Kerr, Michael Clemente, Freja Ebeling, Hanna Rajala, Oscar Brück, Harri Lähdesmäki, Sari Hannula, Tiina Hannunen, Pekka Ellonen, Neal S. Young, Seishi Ogawa, Jaroslaw P. Maciejewski, Eva Hellström-Lindberg, Satu Mustjoki
Published in: Leukemia, 2021, ISSN 0887-6924
Publisher: Nature Publishing Group
DOI: 10.1038/s41375-021-01231-3

Thesis and dissertations (3)

Somatic mutations in autoimmunity

Author(s): Paula Savola
Published in: 2019
Publisher: University of Helsinki

Targeting Key Survival Signaling Pathways for the Treatment of Leukemia

Author(s): Heikki Kuusanmaki
Published in: 2018
Publisher: University of Helsinki

Characterization of mature T-cell leukemias by next-generation sequencing and drug sensitivity testing

Author(s): Emma I Andersson
Published in: 2017
Publisher: University of Helsinki