Article
Hematology
Te Ling, Kevin Zhang, Jiayue Yang, Sandeep Gurbuxani, John D. Crispino
Summary: GATA1 mutations leading to the loss of N-terminal 83 amino acids are observed in various diseases, including myeloid leukemia in children with Down syndrome and certain types of anemia. A mouse model, expressing only the short GATA1 isoform, has been used to study hematopoiesis defects during gestation. However, this study demonstrates that Gata1s mutant mice display macrocytic anemia and abnormal megakaryopoiesis throughout their lifespan, suggesting the potential use of this model for GATA1 deficiency studies.
Article
Biochemistry & Molecular Biology
Anthony Fernandez-Castaneda, Peiwen Lu, Anna C. Geraghty, Eric Song, Myoung-Hwa Lee, Jamie Wood, Michael R. O'Dea, Selena Dutton, Kiarash Shamardani, Kamsi Nwangwu, Rebecca Mancusi, Belgin Yalcin, Kathryn R. Taylor, Lehi Acosta-Alvarez, Karen Malacon, Michael B. Keough, Lijun Ni, Pamelyn J. Woo, Daniel Contreras-Esquivel, Angus Martin Shaw Toland, Jeff R. Gehlhausen, Jon Klein, Takehiro Takahashi, Julio Silva, Benjamin Israelow, Carolina Lucas, Tianyang Mao, Mario A. Pena-Hernandez, Alexandra Tabachnikova, Robert J. Homer, Laura Tabacof, Jenna Tosto-Mancuso, Erica Breyman, Amy Kontorovich, Dayna McCarthy, Martha Quezado, Hannes Vogel, Marco M. Hefti, Daniel P. Perl, Shane Liddelow, Rebecca Folkerth, David Putrino, Avindra Nath, Akiko Iwasaki, Michelle Monje
Summary: COVID survivors may experience lingering neurological symptoms similar to cognitive impairment related to cancer therapy. Research has found that respiratory SARS-CoV-2 infection can cause white-matter-selective microglial reactivity and affect neurogenesis and CCL11 levels.
Article
Immunology
Siavash Mashhouri, Petya Koleva, Mai Huynh, Isobel Okoye, Shima Shahbaz, Shokrollah Elahi
Summary: This study revealed significant sexual dimorphism in CECs, with female mice and human females exhibiting higher levels of CECs compared to males. CECs, particularly their progenitors CD45+CECs, showed enhanced immunomodulatory properties, suppressing T cell activation and proliferation through L-arginine depletion. The abundance of CECs in anemic mice and post-menstrual cycle women may contribute to immune suppression and susceptibility to infections like Bordetella pertussis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Hikaru Kanemasa, Masataka Ishimura, Katsuhide Eguchi, Tamami Tanaka, Etsuro Nanishi, Akira Shiraishi, Motohiro Goto, Yoshitomo Motomura, Shouichi Ohga
Summary: CECs in SoJIA patients exhibit upregulated erythropoiesis-related genes and represent the largest expansion among other inflammatory diseases. Their levels correlate with inflammatory markers, and they may control excessive inflammation via immunoregulatory pathways involving arginase-2.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Koichi Murakami, Haruka Sasaki, Akira Nishiyama, Daisuke Kurotaki, Wataru Kawase, Tatsuma Ban, Jun Nakabayashi, Satoko Kanzaki, Yoichi Sekita, Hideaki Nakajima, Keiko Ozato, Tohru Kimura, Tomohiko Tamura
Summary: IRF8 transcription factor regulates lineage choice in the myeloid cell system in a dose-dependent manner through epigenetic regulation of distinct sets of enhancers in cooperation with other transcription factors.
Article
Microbiology
Anne Sophie Lagneaux, Sandrine Henard, Laure Diancourt, Emmanuelle Stein, Pierre Perez, Pierre Mathieu, Corentine Alauzet, Alain Lozniewski
Summary: Clostridium haemolyticum is a fastidious anaerobe that can cause severe infections in humans, leading to hemolysis and other complications. While rare, infections caused by this organism should be considered in febrile patients with severe hemolytic anemia for prompt diagnosis and treatment.
Article
Hematology
Raymond T. Doty, Xiaowei Yan, Changting Meng, Christopher Lausted, Qiang Tian, Janis L. Abkowitz
Summary: This study fully characterized Rpl11 haploinsufficient mice as a model of DBA, showing similarities to the macrocytic anemia seen in DBA patients. The researchers found that heme excess and toxicity were the primary drivers of this anemia, and identified pathways associated with erythroid differentiation impairment. These findings suggest that Rpl11 haploinsufficient mice can be used as a valuable model to study DBA pathogenesis and test novel therapies.
EXPERIMENTAL HEMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Allison L. Fisher, Veena Sangkhae, Kamila Balusikova, Nicolaos J. Palaskas, Tomas Ganz, Elizabeta Nemeth
Summary: Iron is essential for embryo and placental development and maternal health during pregnancy, but excess maternal iron can lead to adverse embryo outcomes in pregnancies with underlying systemic inflammation, as demonstrated in a study using mouse models.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Hironari Nishizawa, Mie Yamanaka, Kazuhiko Igarashi
Summary: Ferroptosis is a form of cell death triggered by intracellular peroxidation of cell membrane phospholipids. It is regulated by transcription factors NRF2 and BACH1, which control various pathways and processes involved in ferroptosis.
Article
Hematology
Daniel A. Arber, Attilio Orazi, Robert P. Hasserjian, Michael J. Borowitz, Katherine R. Calvo, Hans-Michael Kvasnicka, Sa A. Wang, Adam Bagg, Tiziano Barbui, Susan Branford, Carlos E. Bueso-Ramos, Jorge E. Cortes, Paola Dal Cin, Courtney D. DiNardo, Herve Dombret, Eric J. Duncavage, Benjamin L. Ebert, Elihu H. Estey, Fabio Facchetti, Kathryn Foucar, Naseema Gangat, Umberto Gianelli, Lucy A. Godley, Nicola Gokbuget, Jason Gotlib, Eva Hellstrom-Lindberg, Gabriela S. Hobbs, Ronald Hoffman, Elias J. Jabbour, Jean-Jacques Kiladjian, Richard A. Larson, Michelle M. Le Beau, Mignon L. -C. Loh, Bob Lowenberg, Elizabeth Macintyre, Luca Malcovati, Charles G. Mullighan, Charlotte Niemeyer, Olatoyosi M. Odenike, Seishi Ogawa, Alberto Orfao, Elli Papaemmanuil, Francesco Passamonti, Kimmo Porkka, Ching-Hon Pui, Jerald P. Radich, Andreas Reiter, Maria Rozman, Martina Rudelius, Michael R. Savona, Charles A. Schiffer, Annette Schmitt-Graeff, Akiko Shimamura, Jorge Sierra, Wendy A. Stock, Richard M. Stone, Martin S. Tallman, Juergen Thiele, Hwei-Fang Tien, Alexandar Tzankov, Alessandro M. Vannucchi, Paresh Vyas, Andrew H. Wei, Olga K. Weinberg, Agnieszka Wierzbowska, Mario Cazzola, Hartmut Dohner, Ayalew Tefferi
Summary: In 2016, the WHO, Society for Hematopathology, and European Association for Haematopathology collaborated to update the classification of myeloid neoplasms and acute leukemias, advancing the field of myeloid neoplasms and acute leukemias.
Editorial Material
Hematology
Attilio Orazi, Robert P. Hasserjian, Mario Cazzola, Hartmut Dohner, Ayalew Tefferi, Daniel A. Arber
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Hideki Makishima, Ryunosuke Saiki, Yasuhito Nannya, Sophia Korotev, Carmelo Gurnari, June Takeda, Yukihide Momozawa, Steve Best, Pramila Krishnamurthy, Tetsuichi Yoshizato, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Yasunobu Nagata, Nobuyuki Kakiuchi, Makoto Onizuka, Kenichi Chiba, Hiroko Tanaka, Ayana Kon, Yotaro Ochi, Masahiro M. Nakagawa, Rurika Okuda, Takuto Mori, Akinori Yoda, Hidehiro Itonaga, Yasushi Miyazaki, Masashi Sanada, Takayuki Ishikawa, Shigeru Chiba, Hisashi Tsurumi, Senji Kasahara, Carsten Mueller-Tidow, Akifumi Takaori-Kondo, Kazuma Ohyashiki, Toru Kiguchi, Fumihiko Matsuda, Joop H. Jansen, Chantana Polprasert, Piers Blombery, Yoichiro Kamatani, Sator Miyano, Luca Malcovati, Torsten Haferlach, Michiaki Kubo, Mario Cazzola, Austin G. Kulasekararaj, Lucy A. Godley, Jaroslaw P. Maclejewski, Seishi Ogawa
Summary: DDX41 gene mutations play an important role in late-onset myeloid neoplasms, but many crucial features of DDX41-mutated neoplasms still need to be elucidated. This study comprehensively characterized DDX41-mutated neoplasms and found that DDX41 risk variants accounted for 80% of known genetic predispositions to myeloid neoplasms in adults. Additionally, DDX41 risk alleles were significantly enriched in Japanese cases and more prominent in males compared to females.
Review
Biochemistry & Molecular Biology
Manuj Ahuja, Navneet Ammal Kaidery, Debashis Dutta, Otis C. Attucks, Eliot H. Kazakov, Irina Gazaryan, Mitsuyo Matsumoto, Kazuhiko Igarashi, Sudarshana M. Sharma, Bobby Thomas
Summary: Parkinson's disease is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons. Although the exact cause is unclear, oxidative stress, mitochondrial dysfunction, neuroinflammation, and disruption of calcium homeostasis have been proposed as contributing factors. While drugs targeting these pathways have shown promise in preclinical models, a more effective therapeutic approach involving the activation of the Nrf2/Bach1 signaling pathway is being explored. This review discusses the potential benefits of simultaneously inhibiting Bach1 and stabilizing Nrf2 for the treatment of Parkinson's disease.
Article
Hematology
Christian Pecquet, Nicolas Papadopoulos, Thomas Balligand, Ilyas Chachoua, Amandine Tisserand, Audrey Nedelec, Didier Vertommen, Anita Roy, Caroline Marty, Harini Nivarthi, Mira El-Khoury, Eva Hug, Andrea Majoros, Erica Xu, Oleh Zagrijtschuk, Tudor E. Fertig, Daciana S. Marta, Heinz Gisslinger, Bettina Gisslinger, Martin Schalling, Ilaria Casetti, Elisa Rumi, Daniela Pietra, Chiara Cavalloni, Luca Arcaini, Mario Cazzola, Norio Komatsu, Yoshihiko Kihara, Yoshitaka Sunami, Yoko Edahiro, Marito Araki, Roman Lesyk, Veronika Buxhofer-Ausch, Sonja Heibl, Florence Pasquier, Violaine Havelange, Isabell Plo, William Vainchenker, Robert Kralovics, Stefan N. Constantinescu
Summary: Mutant CALR proteins bind to and activate the TpoR in cells, driving the development of myeloproliferative neoplasms. These mutant CALR proteins can be found in patient plasma complexed with sTFR1, which increases their stability. They can specifically interact with TpoR on target cells and promote thrombopoietin-independent colony formation.
Article
Hematology
Krzysztof Madry, Karol Lis, Pierre Fenaux, David Bowen, Argiris Symeonidis, Moshe Mittelman, Reinhard Stauder, Jaroslav Cermak, Guillermo Sanz, Eva Hellstrom-Lindberg, Saskia Langemeijer, Luca Malcovati, Ulrich Germing, Mette Skov Holm, Agnes Guerci-Bresler, Dominic Culligan, Laurence Sanhes, Ioannis Kotsianidis, Corine van Marrewijk, Simon Crouch, Theo de Witte, Alex Smith
Summary: Information on causes of death and the impact of myelodysplastic syndromes (MDS) on survival in patients with lower-risk MDS is limited. This study shows that MDS and its related complications play a crucial role in the outcome of patients with lower-risk MDS.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Masatoshi Ikeda, Hiroki Kato, Hiroki Shima, Mitsuyo Matsumoto, Eijiro Furukawa, Yan Yan, Ruiqi Liao, Jian Xu, Akihiko Muto, Tohru Fujiwara, Hideo Harigae, Emery H. Bresnick, Kazuhiko Igarashi
Summary: Iron deficiency promotes mitochondrial retention in red blood cells, while heme promotes mitochondrial clearance and erythroblast differentiation. The transcription factor GATA1 regulates autophagy and induces mitophagy through a heme-dependent mechanism. This mechanism provides a molecular framework for understanding this important cell biological process.
EXPERIMENTAL HEMATOLOGY
(2023)
Editorial Material
Hematology
Mario Cazzola
Article
Biochemistry & Molecular Biology
Riko Irikura, Hironari Nishizawa, Kazuma Nakajima, Mie Yamanaka, Guan Chen, Kozo Tanaka, Masafumi Onodera, Mitsuyo Matsumoto, Kazuhiko Igarashi
Summary: Ferroptosis is a regulated cell death induced by iron-dependent lipid peroxidation. The heme-responsive transcription factor BTB and CNC homology 1 (BACH1) promotes ferroptosis by repressing the transcription of genes involved in glutathione (GSH) synthesis and intracellular labile iron metabolism. BACH1 re-expression induced ferroptosis in Bach1(-/-) iMEFs, and the target genes of BACH1 may vary across different cell types and animal species. Furthermore, BACH1 re-expression exhibited a propagating effect and represents a new strategy for inducing ferroptosis.
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Hematology
Koki Nagai, Tetsuya Niihori, Akihiko Muto, Yoshikazu Hayashi, Taiki Abe, Kazuhiko Igarashi, Yoko Aoki
Summary: Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome caused by missense mutations in the MECOM gene. Knockin mice harboring RUSAT-associated MECOM mutations recapitulate the bone marrow dysfunction observed in RUSAT patients.
Review
Immunology
Kyoko Ochiai, Kazuhiko Igarashi
Summary: BACH2 is a transcriptional repressor that regulates gene expression in B cells, promoting antibody class switch and affinity maturation while repressing plasma-cell differentiation. Recent studies suggest that BACH2 may have diverse functions, including gene activation. Understanding these new functions could provide insights into preventing human immune deficiencies.
INTERNATIONAL IMMUNOLOGY
(2023)
Article
Hematology
Georgios Asimomitis, Andre G. Deslaurnes, Andriana G. Kotini, Elsa Bernard, Davide Esposito, Malgorzata Olszewska, Nikolaos Spyrou, Juan Arango Ossa, Teresa Mortera-Blanco, Richard Koche, Luca Malcovati, Seishi Ogawa, Mario Cazzola, Stuart A. Aaronson, Eva Hellstro-Lindberg, Elli Papaemmanuil, Yasuhito Nannya, Eirini P. Papapetrou
Summary: This study provides a comprehensive characterization of the transcriptional and chromatin landscape of SF3B1(K700E) HSPCs and identifies novel mis-spliced genes and transcriptional programs with potential roles in MDS-RS disease biology. Additionally, the study suggests a potential transcriptional regulatory role of the TEAD transcription factor family in SF3B1K700E cells, independent of the Hippo pathway.