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Primary myelofibrosis (PMF) is a clonal hematologic malignancy characterized by BM fibrosis, extramedullary hematopoiesis, circulating CD34+ cells, splenomegaly, and a propensity to evolve to acute myeloid leukemia. Moreover, the spleen and BM of patients harbor atypical, clustered megakaryocytes, which contribute to the disease by secreting profibrotic cytokines. Here, we have revealed that megakaryocytes in PMF show impaired maturation that is associated with reduced GATA1 protein. In investigating the cause of GATA1 downregulation, our gene-expression study revealed the presence of the RPS14-deficient gene signature, which is associated with defective ribosomal protein function and linked to the erythroid lineage in 5q deletion myelodysplastic syndrome. Surprisingly, reduced GATA1 expression and impaired differentiation were limited to megakaryocytes, consistent with a proproliferative effect of a GATA1 deficiency on this lineage. Importantly, expression of GATA1 effectively rescued maturation of PMF megakaryocytes. Together, these results suggest that ribosomal deficiency contributes to impaired megakaryopoiesis in myeloproliferative neoplasms.

The Journal of clinical investigation, 2017-04, Vol.127 (4), p.1316-1320

Downregulation of GATA1 drives impaired hematopoiesis in primary myelofibrosis

Stem Cells Translational Medicine could not maintain its standard of excellence without the invaluable contributions of its dedicated editors and reviewers. Abreu, Maria Abujarour, Ramzey Acosta, Sandra Adams, Gregor Aguilar, Cristobal Ahearne, Mark Ahmad, Faizzan Ahmad, Iqbal Ahmad, Sajjad Aizman, Irina Akutsu, Hidenori Alaminos, Miguel Aldskogius, Hakan Alev, Cantas Alexander, Robert Alhurani, Rabe Ali, Gibran Ali, Hamad Alini, Mauro Alsberg, Eben Alvaro Galue, Eduardo Anagnou, Nicholas Andrade, Nara Andressen, Christian Anjos-Afonso, Fernando Anseth, Kristi Anversa, Piero Anzalone, Rita Aran, Josep Arauzo Bravo, Marcos Armstrong, Lyle Aroom, Kevin Askenasy, Nadir Atala, Anthony Awe, Jason Balasubramanian, D. Balber, Andrew Balkan, Wayne Banasavadi, Yeshavanth Barberi, Tiziano Barish, Michael Bartel, Rhonda Basso, Giuseppe Bauer, Gerhard Becker, Silke Benjamin, Ivor Berry-Caban, Cristobal Berry, Suzanne Berthod, François Bharti, Kapil Bian, Shian Bianchi, Giacomo Bilican, Bilada Blais, Mathieu Blum, Arnon Blurton-Jones, Mathew Boehm, Manfred Bogeska, Ruzhica Bollini, Sveva Bonaldo, Paolo Bonder, Claudine Bonfanti, Paola Bornhauser, Martine Bouhassira, Eric Braunstein, Evan Broccoli, Vania Brodsky, Robert Buchholz, David Bugarski, Diana Bussolati, Benedetta Busson, Elodie Bustos, Martha Byrne, James Cadau, Sébastien Cai, Jun Cai, Mi Caiazzo, Massimiliano Cairo, Mitch Cantz, Tobias Cao, Yi lin Caplan, Arnold Cardier, Jose Carlessi, Luigi Carpenter, Melissa Carr-Wilkinson, Jane Carr, Amanda-Jayne Case, Casey Cavazzano-Calvo, Marina Chao, Nelson Chaubey, Sushma Chen, Yen Shun Cheng, Linzhao Childers, Martin Chintawar, Satyan Chiu, Ing-Ming Chou, Jeffrey Christians, Elisabeth Chung, Choon Cimato, Thomas Coleman, Natalia Connor, Bronwen Coppes, Robert Couture, Larry Csete, Marie Curley, Gerard Cvekl, Ales Dahl, Shannon Danilkovitch, Alla Das, Shreyasi Davis, Alan Day, Richard De Coppi, Paolo de Kruijf, Evert-Jan de la Garza, Anabel Deans, Robert DeFilippo, Roger Dekel, Benjamin Del Debbio, Carolina Delaney, Colleen Deng, Hongkui Deskins, Desirae Detante, Olivier Ding, Sheng Doillon, Charles Dragunow, Mike Dregalla, Ryan Du, Yiqin Duan, Yuyou Dusserre, Nathalie Dyer, Michael Dzau, Victor Dzhoyashvili, Nina Eaker, Shannon Ehrhart-Bornstein, Monika Elkabetz, Yechiel Enosawa, Shin Fehlings, Michael Ferretti, Patrizia Fibbe, Willem Fisk, Nicholas Forristal, Catherine Fox, Ira Frangogiannis, Nikolaos Fujii, Isao Galipeau, Jacques Gan, Qini Gangenahalli, Gurudutta Ganz, Javier Gazit, Roi Gearhart, John P. Genetos, Damian Gentili, Chiara Gerecht, Sharon Gerson, Stanton Giebel, Bernd Gimble, Jeffrey Glass, Nicholas Goh, Pollyanna Goligorsky, Michael Grayson, Warren Gregory, Carl Grottkau, Brian Guillot, Pascale Habibollah, Saba Hamdi, Amir Han, Jinnuo Hanjaya-Putra, Donny Haraguchi, Yuji Hare, Joshua Hariri, Robert Hasegawa, Koji Hattiangady, Bharathi He, Yingbo He, Zhigang Herzberg, Uri Hijaz, Adonis Hirai, Hiroyuki Hosseinkhani, Mohsen Hsu, Shu-Ching Hu, Shijun Huang, Taosheng Huard, Johnny Hursh, Deborah Hyun, Jeong Ichim, Christine Iezzi, Giandomenica Ikeda, Yasuhiro Ikegame, Yuka Inoue, Haruhisa Iso, Yoshitaka Ivanovic, Zoran Jaconi, Marisa Jenkin, Graham Jiang, Wei Jin, Zi-Bing Joe, Aaron Jumabay, Medet Kahler, David Kale, Ajay Kan, Yuet Kanai, Ryuichi Kanczkowski, Waldemar Kaneko, Shin Kang, Jiuhong Karakikes, Ioannis Katz, Adam J. Kaufman, Dan Kaushal, Sunjay Keating, Armand Kelly, Edward Khaldoyanidi, Sophia Knorr, David Koh, Eugene Komatsu, Kenichi Koudstaal, Stefan Kozlova, Elena Krause, Ulf Krawetz, Roman Krueger, Winfried Kuo, Alfred Kurtzberg, Joanne Laitinen, Saara Lako, Majlinda Lamirault, Guillaume Lanza, Robert LaPointe, Vanessa Lappin, Terry R.J. Lazic, Emilija Lazzari, Lorenza Lebkowski, Jane S. Lee, Antonio Lee, Jae Lefaucheur, Louis Lemoli, Roberto Lensch, M. William Lerman, Lilach Lewis, Fiona L'Heureux, Nicolas Li, Xiaowei Lin, Edward Linard, Christine Liu, Jun Liu, Wei Liu, Xuefeng Llull, Ramon Loeken, Mary Loewendorf, Andrea Loring, Jeanne Losordo, Douglas Lowdell, Mark Lowry, William Lynch, Patrick Lysy, Philippe Macchiarini, Paolo Machado, Heather Maehr, Rene Malaterre, Jordane Manetti, Mirko Mao, Hai-Quan Mariappan, Indumathi Marie, Pierre Marra, Kacey Marsell, Richard Martin, Angel Maruotti, Julien Mayani, Hector McKinney-Freeman, Shannon McNiece, Ian Meeson, Annette Mei, Hong Migliaccio, AnnaRita Milan, Gabriella Miller, S. Mills, Kevin Morgan, Michael Morigi, Marina Mosca, Joseph Mosna, Federico Muench, Marcus Müller, Hans Werner Namba, Hiroki Nicaise, Charles Nigam, Sanjay Nishimura, Ken Offen, Daniel Okamoto, Satoshi Okano, Hideyuki Okano, Teruo Oommen, Saji Orlandi, Augusto Orschell, Christie Osakada, Fumitaka Ouyang, Hongwei Panchision, David Panetta, Nicholas Park, Dongsu Park, Katya Pastori, Ricardo Pébay, Alice Pelekanos, Rebecca Peltz, Gary Peng, Hui Penn, Marc Perlingeiro, Rita Peterson, Daniel Petz, Lawrence Pinxteren, Jef Pinzani, Massimo Pitaru, Sandu Pittenger, Mark Pontone, Stefano Prockop, Darwin Quiñones-Hinojosa, Alfredo Rameshwar, Pranela Randolph, Mark Rao, Mahendra Reijo-Pera, Renee Reinders, Marlies Ricordi, Camillo Robey, Pamela Rodrigues, Neil Rodriguez, Clara Roelen, Bernard Rogers, Ian Rogister, Bernard Rosmaninho-Salgado, Joana Ross, James Roubelakis, Maria Rust, Will Sanie-Jahromi, Fatemeh Sartiani, Laura Scadden, David Scheding, Stefan Scheiner, Zachary Schiedlmeier, Bernhard Schmidt, Nils Ole Schrepfer, Sonja Schulman, Ivonne Scruggs, Brittni Sebastiano, Vittorio Sehl, Mary Sekiya, Ichiro Semon, Julie Serikov, Vladimir Sgodda, Malte Sgubin, Donatella Shehadeh, Lina Shen, Wei Sherley, James Shi, Yufang Shinoka, Toshiharu Skardal, Aleksander Slavin, Shimon Soker, Shay Sondergaard, Claus Sowden, Jane Spiegel, Allen M. Srour, Edward Stachowiak, Michal Stacpoole, Sybil Stuiver, Ingrid Sundararaman, Srividya Tedesco, Saverio Tholpady, Sunil Tian, Qiang Ting, Anthony Trounson, Alan O. Tse, Hung Fat Tuan, Rocky Tucker, Budd Uchida, Nobuko van Vlerken, Lilian Vandekerckhove, Bart Veiga, Anna Velpula, Kiran Vessal, Mani Villarin, Balta Vinken, Mathieu Viswanathan, Sowmya Vunjak-Novakovic, Gordana Wakimoto, Hiroaki Wan, Derrick Wang, Fu-Sheng Weir, Gordon Weisdorf, Daniel Whittemore, Scott Williams, Michelle Yaffe, Michael Yamada, Yasuhiro Yamaza, Takayoshi Yang, Nan Yang, Peixin Yang, Shang-Hsun Yang, Wenli Yokoo, Takashi Yu, Vionnie Yuen, Darren Zannettino, Andrew Zhang, Haojian Zhang, Lingjiao Zhang, Mei Zhao, Ting Zhou, Wenyu Zhu, Saiyong Zwaginga, Jaap Jan

Stem cells translational medicine, 2013-12, Vol.2 (12), p.1023-1024

Volume 2 Acknowledgments

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Downregulation of GATA1 drives impaired hematopoiesis in primary myelofibrosis

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