Review
Cell Biology
Grace Egan, Aaron D. Schimmer
Summary: Acute myeloid leukemia (AML), a malignant disease, is driven by somatic mutations. Unique mitochondrial and metabolic dependencies, including reliance on oxidative phosphorylation, have been identified in AML and AML stem cells. Metabolic enzymes have recently been found to play noncanonical roles in regulating gene expression, cell differentiation, and stemness in AML. These mitochondrial and metabolic adaptations are independent of underlying genomic abnormalities and contribute to chemoresistance and relapse.
TRENDS IN CELL BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Ashwin Kishtagari, Ross L. Levine
Summary: AML is characterized by genetic and epigenetic aberrations, with mutations acquired stepwise. Understanding the pathogenesis of AML informs the development of prognostic models and therapeutic strategies.
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2021)
Article
Multidisciplinary Sciences
Naomi Kawashima, Yuichi Ishikawa, Jeong Hui Kim, Yoko Ushijima, Akimi Akashi, Yohei Yamaguchi, Hikaru Hattori, Marie Nakashima, Seara Ikeno, Rika Kihara, Takahiro Nishiyama, Takanobu Morishita, Koichi Watamoto, Yukiyasu Ozawa, Kunio Kitamura, Hitoshi Kiyoi
Summary: The clonal dynamics and selection mechanisms in patient-derived xenografts (PDX) of acute myeloid leukemia (AML) are not fully understood. In this study, the authors generated 160 AML-PDX models to track the clonal dynamics of primary and relapsed AML, finding selectively enriched subclones associated with therapy resistance.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Duolan Naren, Tianyou Yan, Yuping Gong, Jingcao Huang, Dan Zhang, Lina Sang, Xue Zheng, Yarong Li
Summary: This study found that high expression of WTAP in AML patients is associated with poor prognosis, and WTAP plays an epigenetic role in AML by regulating cell proliferation, tumorigenesis, cell cycle, and differentiation. The research also indicated that WTAP makes AML cells resistant to daunorubicin.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Genetics & Heredity
Arevik Ghazaryan, Jared A. Wallace, William W. Tang, Cindy Barba, Soh-Hyun Lee, Kaylyn M. Bauer, Morgan C. Nelson, Carissa N. Kim, Chris Stubben, Warren P. Voth, Dinesh S. Rao, Ryan M. O'Connell
Summary: Acute myeloid leukemia (AML) is a deadly disease characterized by uncontrolled expansion of malignant blasts. This study reveals that blocking pyruvate entry into mitochondria in AML cells decreases oxidative phosphorylation and increases miR-1 expression. Higher miR-1 expression correlates with reduced survival in AML patients. The overexpression of miR-1 promotes AML cell metabolism and exacerbates disease progression in a mouse model, suggesting miR-1 as a potential therapeutic target.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Valentina Giudice, Marisa Gorrese, Rosa Vitolo, Angela Bertolini, Rossella Marcucci, Bianca Serio, Roberto Guariglia, Idalucia Ferrara, Rita Pepe, Francesca D'Alto, Barbara Izzo, Antonio Pedicini, Nunzia Montuori, Maddalena Langella, Carmine Selleri
Summary: WT1 expression levels in AML and MDS inversely correlated with normal hematopoiesis and were positively associated with blast counts. Flow cytometry was shown to be more sensitive and specific in distinguishing normal myeloid cells from neoplastic counterpart, even with just linear parameters and CD45 expression. A simple integrated approach combining blast counts by flow cytometry, FLT3 mutational status, and WT1 expression levels may provide a better prognostic definition for both AML and MDS patients.
Article
Oncology
Toru Kiguchi, Masaki Yamaguchi, Naoki Takezako, Shuichi Miyawaki, Koichi Masui, Yuichiro Ihara, Masao Hirota, Naoko Shimofurutani, Tomoki Naoe
Summary: Although treatment with OCV-501 did not prolong DFS for elderly AML patients, post hoc analysis found that immune responders to OCV-501 whose specific IgG was > 10,000 ng/mL (N = 16) and whose WT1-specific interferon-gamma response was > 10 pg/mL (N = 26) had significantly longer overall survival compared with placebo. The placebo-controlled design of this study and quantitative immunological monitoring provides new insight into the relationship between peptide-induced immune responses and survival, suggesting future perspectives for cancer immunotherapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Dao-Xing Deng, Juan-Juan Wen, Yi-Fei Cheng, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Yu-Hong Chen, Huan Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Ya-Zhen Qin, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Su Zhao, Xiao-Dong Mo
Summary: Sequential monitoring of WT1 after allo-HSCT can predict relapse in pediatric AML, and WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.
Article
Oncology
Yin Wang, Wen-Jun Weng, Dun-Hua Zhou, Jian-Pei Fang, Srishti Mishra, Li Chai, Lu-Hong Xu
Summary: WT1 mutations are associated with poor prognosis in pediatric AML, especially when co-occurring with FLT3/ITD mutations. Hematopoietic stem cell transplantation may improve the prognosis of patients with WT1 mutations.
FRONTIERS IN ONCOLOGY
(2021)
Review
Immunology
Michela Luciano, Peter W. Krenn, Jutta Horejs-Hoeck
Summary: Acute myeloid leukemia (AML) is a heterogeneous blood cancer with complex disease characteristics and cytokine networks, making treatment challenging. The development of new targeted therapies and understanding the functions of cytokines are important for improving treatment options.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Hannah J. Uckelmann, Elena L. Haarer, Reina Takeda, Eric M. Wong, Charlie Hatton, Christian Marinaccio, Florian Perner, Masooma Rajput, Noa J. C. Antonissen, Yanhe Wen, Lu Yang, Lorenzo Brunetti, Chun -Wei Chen, Scott A. Armstrong
Summary: The dysregulation of developmental and stem cell-associated genes is a common phenomenon during cancer development. Most patients with acute myeloid leukemia (AML) express high levels of HOXA cluster genes and MEIS1, with an NPM1 mutation (NPM1c) being common in these cases. This study reveals that NPM1c directly binds to specific chromatin targets, collaborates with the MLL1 complex, and directly regulates oncogenic gene expression in AML.
Review
Genetics & Heredity
Derya Demir
Summary: As our understanding of the biologic basis of acute myeloid leukemia evolves, so do the classification systems used to describe this group of cancers. Recently, two new systems, the International Consensus Classification system and the 5th edition of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues, were published to incorporate the latest genomic advances in blood cancer. This article reviews the major updates in acute myeloid leukemia in both systems and highlights the biologic insights that have driven these changes.
Review
Cell Biology
Jan Philipp Bewersdorf, Omar Abdel-Wahab
Summary: This review discusses the development of promising new molecular targeted approaches for AML, as well as progress in immune targeting of AML through various antibodies and cellular therapies. Despite FDA approval of new drugs for AML, it remains a major area of unmet medical need among hematologic malignancies.
GENES & DEVELOPMENT
(2022)
Article
Multidisciplinary Sciences
Jianming Shao, Sihan Wang, Diana West-Szymanski, Jason Karpus, Shilpan Shah, Siddhartha Ganguly, Janice Smith, Youli Zu, Chuan He, Zejuan Li
Summary: This study conducted a genome-wide analysis of 5-hydroxymethylcytosine (5hmC) in plasma cell-free DNA (cfDNA) of acute myeloid leukemia (AML) patients and non-cancer controls using a highly sensitive technology. The study developed a 5hmC diagnostic model that accurately differentiates AML patients from controls, and a 5hmC prognostic model that predicts prognosis in AML patients. Additionally, the study identified critical genes and pathways related to AML diagnosis and prognosis.
SCIENTIFIC REPORTS
(2022)
Review
Oncology
Kristine Yttersian Sletta, Oriol Castells, Bjorn Tore Gjertsen
Summary: CSF1R is considered as a potential therapeutic target for AML due to its role in regulating plasticity of tumor-associated macrophages. Preclinical research supports the idea that CSF1R-targeted therapy may enhance the effectiveness of conventional and novel therapeutics. The experimental evidence positioning CSF1R inhibitors as treatment for AML should facilitate the translation and clinical development in the future.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Thomas Prebet, Zhuoxin Sun, Rhett P. Ketterling, Amer Zeidan, Peter Greenberg, James Herman, Mark Juckett, Mitchell R. Smith, Lisa Malick, Elisabeth Paietta, Magdalena Czader, Maria Figueroa, Janice Gabrilove, Harry P. Erba, Martin S. Tallman, Mark Litzow, Steven D. Gore
BRITISH JOURNAL OF HAEMATOLOGY
(2016)
Article
Hematology
Coline Gaillard, Taku A. Tokuyasu, Galit Rosen, Jason Sotzen, Adeline Vitaliano-Prunier, Ritu Roy, Emmanuelle Passegue, Hugues de The, Maria E. Figueroa, Scott C. Kogan
Article
Medicine, Research & Experimental
Sun-Mi Park, Mithat Goenen, Ly Vu, Gerard Minuesa, Patrick Tivnan, Trevor S. Barlowe, James Taggart, Yuheng Lu, Raquel R. Deering, Nir Hacohen, Maria E. Figueroa, Elisabeth Paietta, Hugo F. Fernandez, Martin S. Tallman, Ari Melnick, Ross Levine, Christina Leslie, Christopher J. Lengner, Michael G. Kharas
JOURNAL OF CLINICAL INVESTIGATION
(2015)
Article
Multidisciplinary Sciences
Jane Merlevede, Nathalie Droin, Tingting Qin, Kristen Meldi, Kenichi Yoshida, Margot Morabito, Emilie Chautard, Didier Auboeuf, Pierre Fenaux, Thorsten Braun, Raphael Itzykson, Stephane de Botton, Bruno Quesnel, Therese Commes, Eric Jourdan, William Vainchenker, Olivier Bernard, Noemie Pata-Merci, Stephanie Solier, Velimir Gayevskiy, Marcel E. Dinger, Mark J. Cowley, Dorothee Selimoglu-Buet, Vincent Meyer, Francois Artiguenave, Jean-Francois Deleuze, Claude Preudhomme, Michael R. Stratton, Ludmil B. Alexandrov, Eric Padron, Seishi Ogawa, Serge Koscielny, Maria Figueroa, Eric Solary
NATURE COMMUNICATIONS
(2016)
Article
Oncology
Sara E. Meyer, Tingting Qin, David E. Muench, Kohei Masuda, Meenakshi Venkatasubramanian, Emily Orr, Lauren Suarez, Steven D. Gore, Ruud Delwel, Elisabeth Paietta, Martin S. Tallman, Hugo Fernandez, Ari Melnick, Michelle M. Le Beau, Scott Kogan, Nathan Salomonis, Maria E. Figueroa, H. Leighton Grimes
Review
Hematology
Raajit Rampal, Maria E. Figueroa
Article
Oncology
A. C. Kramer, A. Kothari, W. C. Wilson, H. Celik, J. Nikitas, C. Mallaney, E. L. Ostrander, E. Eultgen, A. Martens, M. C. Valentine, A. L. Young, T. E. Druley, M. E. Figueroa, B. Zhang, G. A. Challen
Article
Oncology
V. Santini, B. Allione, G. Zini, D. Gioia, M. Lunghi, A. Poloni, D. Cilloni, A. Sanna, E. Masiera, M. Ceccarelli, O. Abdel-Wahab, A. Terenzi, E. Angelucci, C. Finelli, F. Onida, A. Pelizzari, D. Ferrero, G. Saglio, M. Figueroa, A. Levis
Article
Multidisciplinary Sciences
Theodore T. Ho, Matthew R. Warr, Emmalee R. Adelman, Olivia M. Lansinger, Johanna Flach, Evgenia V. Verovskaya, Maria E. Figueroa, Emmanuelle Passegue
Article
Oncology
Jacob L. Glass, Duane Hassane, Bas J. Wouters, Hiroyoshi Kunimoto, Roberto Avellino, Francine E. Garrett-Bakelman, Olga A. Guryanova, Robert Bowman, Shira Redlich, Andrew M. Intlekofer, Cem Meydan, Tingting Qin, Mame Fall, Alicia Alonso, Monica L. Guzman, Peter J. M. Valk, Craig B. Thompson, Ross Levine, Olivier Elemento, Ruud Delwel, Ari Melnick, Maria E. Figueroa
Article
Multidisciplinary Sciences
Ho Lam Chan, Felipe Beckedorff, Yusheng Zhang, Jenaro Garcia-Huidobro, Hua Jiang, Antonio Colaprico, Daniel Bilbao, Maria E. Figueroa, John LaCava, Ramin Shiekhattar, Lluis Morey
NATURE COMMUNICATIONS
(2018)
Article
Oncology
Pilar M. Dominguez, Hussein Ghamlouch, Wojciech Rosikiewicz, Parveen Kumar, Wendy Beguelin, Lorena Fontan, Martin A. Rivas, Patrycja Pawlikowska, Marine Armand, Enguerran Mouly, Miguel Torres-Martin, Ashley S. Doane, Maria T. Calvo Fernandez, Matt Durant, Veronique Della-Valle, Matt Teater, Luisa Cimmino, Nathalie Droin, Saber Tadros, Samaneh Motanagh, Alan H. Shih, Mark A. Rubin, Wayne Tam, Iannis Aifantis, Ross L. Levine, Olivier Elemento, Giorgio Inghirami, Michael R. Green, Maria E. Figueroas, Olivier A. Bernard, Said Aoufouchi, Sheng Li, Rita Shaknovich, Ari M. Melnick
Review
Hematology
Hsuan-Ting Huang, Maria E. Figueroa
Summary: Epigenetic deregulation is a recognized mechanism in the development of myeloid malignancies, with studies showing patterns of aberrant DNA methylation, altered chromatin states, and mutations in chromatin modifiers. Understanding these disease mechanisms can lead to new therapeutic interventions, especially in the context of existing chemotherapy standards.
Article
Biochemistry & Molecular Biology
Luisa Cimmino, Igor Dolgalev, Yubao Wang, Akihide Yoshimi, Gaelle H. Martin, Jingjing Wang, Victor Ng, Bo Xia, Matthew T. Witkowski, Marisa Mitchell-Flack, Isabella Grillo, Sofia Bakogianni, Delphine Ndiaye-Lobry, Miguel Torres Martin, Maria Guillamot, Robert S. Banh, Mingjiang Xu, Maria E. Figueroa, Ross A. Dickins, Omar Abdel-Wahab, Christopher Y. Park, Aristotelis Tsirigos, Benjamin G. Neel, Iannis Aifantis
