Article
Medicine, Research & Experimental
Beatrice Bocquet, Caroline Borday, Nejla Erkilic, Daria Mamaeva, Alicia Donval, Christel Masson, Karine Parain, Karolina Kaminska, Mathieu Quinodoz, Irene Perea-Romero, Gema Garcia-Garcia, Carla Jimenez-Medina, Hassan Boukhaddaoui, Arthur Coget, Nicolas Leboucq, Giacomo Calzetti, Stefano Gandolfi, Antonio Percesepe, Valeria Barili, Vera Uliana, Marco Delsante, Francesca Bozzetti, Hendrik P. N. Scholl, Marta Corton, Carmen Ayuso, Jose M. Millan, Carlo Rivolta, Isabelle Meunier, Muriel Perron, Vasiliki Kalatzis
Summary: The study reveals that mutations in the TBC1D32 gene may lead to RP, highlighting its critical role in retinal development and function.
Article
Medicine, Research & Experimental
Eva Lausberg, Sebastian Giesselmann, Joseph P. Dewulf, Elsa Wiame, Anja Holz, Ramona Salvarinova, Clara D. van Karnebeek, Patricia Klemm, Kim Ohl, Michael Mull, Till Braunschweig, Joachim Weis, Clemens J. Sommer, Stephanie Demuth, Claudia Haase, Claudia Stollbrink-Peschgens, Francois-Guillaume Debray, Cecile Libioulle, Daniela Choukair, Prasad T. Oommen, Arndt Borkhardt, Harald Surowy, Dagmar Wieczorek, Norbert Wagner, Robert Meyer, Thomas Eggermann, Matthias Begemann, Emile Van Schaftingen, Martin Hausler, Klaus Tenbrock, Lambert van den Heuvel, Miriam Elbracht, Ingo Kurth, Florian Kraft
Summary: Our study reveals that C2orf69 is associated with brain abnormalities, liver dysfunction, and recurrent autoinflammation, as well as influencing mitochondrial function and glycogen metabolism.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Hematology
Alexander J. Willis, Seth J. Corey, Carlos Murga-Zamalloa, Saman S. Karimi, Karam Khaddour, John Quigley, Elizabeth A. Eklund, Yolande Chen
Summary: This study demonstrates that female mice with BM Dnm2 haploinsufficiency develop neutropenia as they age, along with decreased white blood cell count and migration defects of neutrophils. These findings provide insights into the potential mechanisms underlying chronic idiopathic neutropenia, a condition predominantly observed in middle-aged women.
Article
Hematology
Teresa D'Altri, Anna S. Wilhelmson, Mikkel B. Schuster, Anne Wenzel, Adrija Kalvisa, Sachin Pundhir, Anne Meldgaard Hansen, Bo T. Porse
Summary: Researchers generated a knockin mouse model with ASXL1 mutation, which accelerated disease development in the context of CEBPA mutation and led to poor response to chemotherapy in mice.
Review
Biochemistry & Molecular Biology
Binsah George, Hagop Kantarjian, Natalia Baran, Joseph Douglas Krocker, Adan Rios
Summary: Mutations in the tumor suppressor gene TP53 are strongly linked to poor survival outcomes in AML patients, particularly in cases with complex cytogenetics or therapy-related AML. Despite the prevalence of TP53 mutations in cancer, targeted therapeutic interventions for these mutations remain limited, highlighting the need for personalized treatment strategies. Understanding the functional differences of p53 mutants is crucial in developing effective therapies for AML patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Melanie Decker, Anupriya Agarwal, Andreas Benneche, Jane Churpek, Nicolas Duployez, Adam Duvall, Martijn P. T. Ernst, Alisa Foerster, Hildegunn Hoberg-Vetti, Inga Hofmann, Michelle Nash, Marc H. G. P. Raaijmakers, Tor H. A. Tvedt, Adrianna Vlachos, Brigitte Schlegelberger, Thomas Illig, Tim Ripperger
Summary: In this study, the applicability of transactivation assays to investigate variants of the RUNX1 protein was evaluated. It was found that C-terminal RUNX1 variants require the development of new assays. Two variants of unknown significance were reclassified as likely pathogenic, and the (likely) pathogenic classification of two other variants was supported. The functionality of four variants of unknown significance was demonstrated, but reclassification to (likely) benign was challenging, indicating the need for reevaluating current classification guidelines. The clinical utility of the assays was illustrated in the context of seven families.
Article
Multidisciplinary Sciences
Giulia Fasano, Valentina Muto, Francesca Clementina Radio, Martina Venditti, Niloufar Mosaddeghzadeh, Simona Coppola, Graziamaria Paradisi, Erika Zara, Farhad Bazgir, Alban Ziegler, Giovanni Chillemi, Lucia Bertuccini, Antonella Tinari, Annalisa Vetro, Francesca Pantaleoni, Simone Pizzi, Libenzio Adrian Conti, Stefania Petrini, Alessandro Bruselles, Ingrid Guarnetti Prandi, Cecilia Mancini, Balasubramanian Chandramouli, Magalie Barth, Celine Bris, Donatella Milani, Angelo Selicorni, Marina Macchiaiolo, Michaela V. Gonfiantini, Andrea Bartuli, Riccardo Mariani, Cynthia J. Curry, Renzo Guerrini, Anne Slavotinek, Maria Iascone, Bruno Dallapiccola, Mohammad Reza Ahmadian, Antonella Lauri, Marco Tartaglia
Summary: Disruption to the ER-Golgi network can cause neurodevelopmental disorders, and ARF3 mutations have been identified as the cause of a rare pediatric neurological disorder. This study provides detailed molecular characterization of ARF3 mutations and demonstrates their impact on Golgi morphology, vesicles assembly, and trafficking.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Barbara Spitzer, Kayleigh D. Rutherford, Gunes Gundem, Erin M. McGovern, Nathan E. Millard, Juan E. Arango Ossa, Irene Y. Cheung, Teng Gao, Max F. Levine, Yanming Zhang, Juan S. Medina-Martinez, Yi Feng, Ryan N. Ptashkin, Kelly L. Bolton, Noushin Farnoud, Yangyu Zhou, Minal A. Patel, Georgios Asimomitis, Cassidy C. Cobbs, Neeman Mohibullah, Kety H. Huberman, Maria E. Arcilla, Brian H. Kushner, Shakeel Modak, Andrew L. Kung, Ahmet Zehir, Ross L. Levine, Scott A. Armstrong, Nai Kong Cheung, Elli Papaemmanuil
Summary: This study aimed to explore the relationship between the development of t-MDS/AL and molecular abnormalities in pediatric patients with high-risk neuroblastoma. The study found that at least one disease-defining alteration was detected in all cases at t-MDS/AL diagnosis, with TP53 gene mutations and KMT2A gene rearrangements being the most common. Compared to the transient and control groups, t-MDS/AL patients had acquired mutations at an earlier stage before the onset of the disease. Additionally, the study revealed that only a small number of pediatric patients with solid tumors had clonal hematopoiesis involving myeloid genes.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Marie-Berengere Troadec, Francoise Porteu, Marie -Laure Arcangeli, Adlen Foudi, Dominique Bluteau, Paulo De Sepulveda, Christel Guillouf, Nathalie M. Mazure, Fabienne Meggetto, Philippe Brunet De La Grange, Cyril Broccardo
Summary: This article summarizes the presentations from the 2021 scientific meeting of the Club Hematopoiesis and Oncogenesis. The meeting focused on hematopoiesis and oncogenic mechanisms, covering topics such as expansion of hematopoietic stem cells, the role of stem cell niches, the intersection of hematology and immunology, the importance of metabolism in hematopoiesis, solid tumors and oncogenesis, the noncoding genome, inflammation in monocyte differentiation and leukemia, as well as recent advances in myeloid malignancies, lymphoid leukemia, and lymphoma.
BULLETIN DU CANCER
(2023)
Article
Multidisciplinary Sciences
Carolina Gracia-Diaz, Yijing Zhou, Qian Yang, Reza Maroofian, Paula Espana-Bonilla, Chul-Hwan Lee, Shuo Zhang, Natalia Padilla, Raquel Fueyo, Elisa Waxman, Sunyimeng Lei, Garrett Otrimski, Dong Li, Sarah Sheppard, Paul Mark, Margaret Harr, Hakon Hakonarson, Lance Rodan, Adam Jackson, Pradeep Vasudevan, Corrina Powel, Shehla Mohammed, Sateesh Maddirevula, Hamad Alzaidan, Eissa Faqeih, Stephanie Efthymiou, Valentina Turchetti, Fatima Rahman, Shazia Maqbool, Vincenzo Salpietro, Shahnaz Ibrahim, Gabriella di Rosa, Henry Houlden, Maha Nasser Alharbi, Nouriya Abbas Al-Sannaa, Peter Bauer, Giovanni Zifarelli, Conchi Estaras, Anna C. E. Hurst, Michelle Thompson, Anna Chassevent, Constance Smith-Hicks, Xavier de la Cruz, Alexander Holtz, Houda Zghal Elloumi, M. J. L. Hajianpour, Claudine A. Rieubland, Dominique Braun, Siddharth Banka, M. J. Genomic England Res Consortium, Deborah L. S. French, Elizabeth B. Heller, Murielle Saade, Hongjun J. Song, Guo-li A. Ming, Fowzan Alkuraya, Pankaj B. Agrawal, Danny Reinberg, Elizabeth J. Bhoj, Marian Martinez-Balbas, Naiara Akizu
Summary: This study identifies pathogenic variants in the chromatin modifier EZH1 as the cause of neurodevelopmental disorders. These variants affect the structure and function of EZH1, leading to impaired neural differentiation. The findings highlight the critical role of EZH1 in neurogenesis regulation and provide molecular diagnosis for previously undefined neurodevelopmental disorders.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Brooks A. Benard, Logan B. Leak, Armon Azizi, Daniel Thomas, Andrew J. Gentles, Ravindra Majeti
Summary: This study aggregates multiple AML cohorts to explore the correlation between clonal abundance of somatic mutations and clinical outcomes. High variant allele frequency for certain mutations is associated with poor prognosis, while increased GATA2 variant allele frequency correlates with better outcomes. Clinical features such as white blood cell count and blast percentage are related to the subclonal abundance of mutations like TP53 and IDH1.
NATURE COMMUNICATIONS
(2021)
Article
Biophysics
Johannes Frasez Soerensen, Anni Aggerholm, Carina Agerbo Rosenberg, Marie Bill, Gitte Birk Kerndrup, Lene Hyldahl Ebbesen, Marcus Hoy Hansen, Anne Stidsholt Roug, Maja Ludvigsen
Summary: Clonal hematopoiesis is associated with an increased risk of therapy-related myeloid neoplasms following autologous stem cell transplantation. Specific mutations have not been fully understood in terms of their impact on the progression from clonal hematopoiesis to myeloid neoplasms. This study used deep sequencing to analyze longitudinal samples and found evidence supporting the hypothesis that clonal hematopoiesis at low variant allele frequencies can lead to the development of myeloid neoplasms following autologous stem cell transplantation.
BONE MARROW TRANSPLANTATION
(2022)
Article
Multidisciplinary Sciences
Nicholas Williams, Joe Lee, Emily Mitchell, Luiza Moore, E. Joanna Baxter, James Hewinson, Kevin J. Dawson, Andrew Menzies, Anna L. Godfrey, Anthony R. Green, Peter J. Campbell, Jyoti Nangalia
Summary: By sequencing the clones of 12 patients with myeloproliferative neoplasms, we identified that early driver mutations are the foundation for tumor development and are linked to lifelong growth and evolution. This discovery provides opportunities for early intervention and a new model for cancer development.
Article
Hematology
Thomas L. Olson, HeeJin Cheon, Jeffrey C. Xing, Kristine C. Olson, Umadevi Paila, Cait E. Hamele, Yaseswini Neelamraju, Bryna C. Shemo, Matt Schmachtenberg, Shriram K. Sundararaman, Mariella F. Toro, Cheryl A. Keller, Emily A. Farber, Suna Onengut-Gumuscu, Francine E. Garrett-Bakelman, Ross C. Hardison, David J. Feith, Aakrosh Ratan, Thomas P. Loughran
Summary: Chronic natural killer large granular lymphocyte (NK-LGL) leukemia is a rare disorder characterized by prolonged expansion of clonal NK cells, with unique mutations such as TET2 and STAT3 playing important roles in its pathogenesis.
Article
Cell Biology
Raghav Ramabadran, Jarey H. Wang, Jaime M. Reyes, Anna G. Guzman, Sinjini Gupta, Carina Rosas, Lorenzo Brunetti, Michael C. Gundry, Ayala Tovy, Hali Long, Tianpeng Gu, Sean M. Cullen, Siddhartha Tyagi, Danielle Rux, Jean J. Kim, Steven M. Kornblau, Michael Kyba, Fabio Stossi, Rachel E. Rau, Koichi Takahashi, Thomas F. Westbrook, Margaret A. Goodell
Summary: Ramabadran et al. discovered that upon extrinsic stimulation, stem cells activate a program involving increased splicing efficiency mediated by DNMT3A and recruitment of SF3B1 to RNA polymerase and mRNA, promoting the activation of embryonic and hematopoietic stem cells. This DNA methylation-independent role of DNMT3A in stem cell activation and splicing regulation provides new insights into the mechanisms governing stem cell differentiation.
NATURE CELL BIOLOGY
(2023)
Article
Hematology
David J. H. F. Knapp, Colin A. Hammond, Nima Aghaeepour, Paul H. Miller, Davide Pellacani, Philip A. Beer, Karen Sachs, Wenlian Qiao, WeiJia Wang, R. Keith Humphries, Guy Sauvageau, Peter W. Zandstra, Sean C. Bendall, Garry P. Nolan, Carl Hansen, Connie J. Eaves
Article
Hematology
Monica Cusan, Naidu M. Vegi, Medhanie A. Mulaw, Shiva Bamezai, Lisa M. Kaiser, Aniruddha J. Deshpande, Philipp A. Greif, Leticia Quintanilla-Fend, Stefanie Goellner, Carsten Mueller-Tidow, Keith R. Humphries, Scott A. Armstrong, Wolfgang Hiddemann, Michaela Feuring-Buske, Christian Buske
Article
Hematology
Paul H. Miller, Gabrielle Rabu, Margarita MacAldaz, David J. H. F. Knapp, Alice M. S. Cheung, Kiran Dhillon, Naoto Nakamichi, Philip A. Beer, Leonard D. Shultz, R. Keith Humphries, Connie J. Eaves
EXPERIMENTAL HEMATOLOGY
(2017)
Editorial Material
Hematology
R. Keith Humphries, Connie Eaves
EXPERIMENTAL HEMATOLOGY
(2017)
Article
Hematology
Edith Schneider, Anna Staffas, Linda Roehner, Erik D. Malmberg, Arghavan Ashouri, Kathrin Krowiorz, Nicole Pochert, Christina Miller, Stella Yuan Wei, Laleh Arabanian, Christian Buske, Hartmut Doehner, Lars Bullinger, Linda Fogelstrand, Michael Heuser, Konstanze Doehner, Ping Xiang, Jens Ruschmann, Oleh I. Petriv, Alireza Heravi-Moussavi, Carl L. Hansen, Martin Hirst, R. Keith Humphries, Arefeh Rouhi, Lars Palmqvist, Florian Kuchenbauer
Article
Hematology
Maura Gasparetto, Shanshan Pei, Mohammad Minhajuddin, Nabilah Khan, Daniel A. Pollyea, Jason R. Myers, John M. Ashton, Michael W. Becker, Vasilis Vasiliou, Keith R. Humphries, Craig T. Jordan, Clayton A. Smith
Article
Oncology
X. Liu, K. Rothe, R. Yen, C. Fruhstorfer, T. Maetzig, M. Chen, D. L. Forrest, R. K. Humphries, X. Jiang
Letter
Oncology
N. Jyotsana, A. Sharma, A. Chaturvedi, M. Scherr, F. Kuchenbauer, L. Sajti, A. Barchanski, R. Lindner, F. Noyan, K-W Suehs, D. Grote-Koska, K. Brand, H-P Vornlocher, M. Stanulla, B. Bornhauser, J-P Bourquin, M. Eder, F. Thol, A. Ganser, R. K. Humphries, E. Ramsay, P. Cullis, M. Heuser
Article
Oncology
M. Mingay, A. Chaturvedi, M. Bilenky, Q. Cao, L. Jackson, T. Hui, M. Moksa, A. Heravi-Moussavi, R. K. Humphries, M. Heuser, M. Hirst
Article
Hematology
Edith Schneider, Anna Staffas, Linda Roehner, Erik D. Malmberg, Arghavan Ashouri, Kathrin Krowiorz, Nicole Pochert, Christina Miller, Stella Yuan Wei, Laleh Arabanian, Christian Buske, Hartmut Doehner, Lars Bullinger, Linda Fogelstrand, Michael Heuser, Konstanze Doehner, Ping Xiang, Jens Ruschmann, Oleh I. Petriv, Alireza Heravi-Moussavi, Carl L. Hansen, Martin Hirst, R. Keith Humphries, Arefeh Rouhi, Lars Palmqvist, Florian Kuchenbauer
Article
Oncology
Raj Bhayadia, Kathrin Krowiorz, Nadine Haetscher, Razan Jammal, Stephan Emmrich, Askar Obulkasim, Jan Fiedler, Adrian Schwarzer, Arefeh Rouhi, Michael Heuser, Susanne Wingert, Sabrina Bothur, Konstanze Doehner, Tobias Maetzig, Michelle Ng, Dirk Reinhardt, Hartmut Doehner, C. Michel Zwaan, Marry van den Heuvel Eibrink, Dirk Heckl, Maarten Fornerod, Thomas Thum, R. Keith Humphries, Michael A. Rieger, Florian Kuchenbauer, Jan-Henning Klusmann
JOURNAL OF CLINICAL ONCOLOGY
(2018)
Article
Cell Biology
David J. H. F. Knapp, Colin A. Hammond, Tony Hui, Marijn T. J. van Loenhout, Fangwu Wang, Nima Aghaeepour, Paul H. Miller, Michelle Moksa, Gabrielle M. Rabu, Philip A. Beer, Davide Pellacani, R. Keith Humphries, Carl Hansen, Martin Hirst, Connie J. Eaves
NATURE CELL BIOLOGY
(2018)
Article
Medicine, Research & Experimental
Mor Ngom, Suzan Imren, Tobias Maetzig, Jennifer E. Adair, David J. H. F. Knapp, Jalila Chagraoui, Iman Fares, Marie-Eve Bordeleau, Guy Sauvageau, Philippe Leboulch, Connie Eaves, Richard Keith Humphries
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2018)
Article
Biochemical Research Methods
Tiam Heydari, Matthew A. Langley, Cynthia W. Fisher, Daniel A. Aguilar-Hidalgo, Shreya Shukla, Ayako A. Yachie-Kinoshita, Michael Hughes, Kelly A. M. McNagny, Peter Zandstra
Summary: This article introduces IQCELL, a platform based on single-cell RNA sequencing data to infer, simulate, and study executable logical gene regulatory networks (GRNs). Using scRNA-seq datasets from mouse T-cell and red blood cell development, IQCELL can infer the majority of previously reported causal gene interactions and simulate the effects of known gene perturbations. It also provides a gene selection pipeline for identifying candidate genes without prior knowledge.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Oncology
Sebastian Mohr, Carmen Doebele, Federico Comoglio, Tobias Berg, Julia Beck, Hanibal Bohnenberger, Gabriela Alexe, Jasmin Corso, Philipp Stroebel, Astrid Wachter, Tim Beissbarth, Frank Schnuetgen, Anjali Cremer, Nadine Haetscher, Stefanie Goellner, Arefeh Rouhi, Lars Palmqvist, Michael A. Rieger, Timm Schroeder, Halvard Boenig, Carsten Meuller-Tidow, Florian Kuchenbauer, Ekkehard Schuetz, Anthony R. Green, Henning Urlaub, Kimberly Stegmaier, R. Keith Humphries, Hubert Serve, Thomas Oellerich