Review
Biochemistry & Molecular Biology
Carmelo Gurnari, Simona Pagliuca, Valeria Visconte
Summary: Research on metabolic deregulation in myeloid malignancies has shown that cells undergoing leukemic transformation have higher energy demands for growth and proliferation, leading to a focus on metabolic-targeted therapies. However, the most difficult challenge is determining a therapeutic window that selectively impacts malignant cells without harming normal cells. It has been found that leukemic cells have unique metabolic features, such as IDH1/2 mutations leading to abnormal metabolite production inhibiting enzyme activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Deirdra Venney, Adone Mohd-Sarip, Ken Mills
Summary: Myeloid malignancy encompasses a range of diseases including MPN, MDS, and AML, with genomic studies revealing numerous somatic mutations and highlighting the importance of epigenetic mutations in disease progression. Key genes like DNMT3A, TET2, ASXL1, EZH2, and IDH1/2 play critical roles in disease pathogenesis. Advances in understanding disease progression, mutational profiles, and therapeutic potential are continually improving our knowledge of myeloid malignancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Tomoya Muto, Maria Guillamot, Jennifer Yeung, Jing Fang, Joshua Bennett, Bettina Nadorp, Audrey Lasry, Luna Zea Redondo, Kwangmin Choi, Yixiao Gong, Callum S. Walker, Kathleen Hueneman, Lyndsey C. Bolanos, Laura Barreyro, Lynn H. Lee, Kenneth D. Greis, Nikita Vasyliev, Alireza Khodadadi-Jamayran, Evgeny Nudler, Amaia Lujambio, Scott W. Lowe, Iannis Aifantis, Daniel T. Starczynowski
Summary: Clonal hematopoiesis (CH) is an aging-associated condition characterized by the clonal outgrowth of pre-leukemic cells that acquire specific mutations. TRAF6, a ubiquitin ligase gene, is identified to cooperate with pre-leukemic cells and its loss leads to overt myeloid leukemia through MYC-dependent stem cell signatures. Repression of TRAF6 signaling can potentially contribute to the development of acute leukemia.
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.
Review
Hematology
Johann-Christoph Jann, Zuzana Tothova
Summary: The cohesin complex plays an essential role in healthy and malignant hematopoiesis, with its mutations recurrently found in various hematologic and solid malignancies. However, the mechanisms by which these mutations drive clonal expansion and disease progression are still poorly understood.
Article
Oncology
Katsuhiro Togami, Sun Sook Chung, Vikas Madan, Christopher A. G. Booth, Christopher M. Kenyon, Lucia Cabal-Hierro, Justin Taylor, Sunhee S. Kim, Gabriel K. Griffin, Mahmoud Ghandi, Jia Li, Yvonne Y. Li, Fanny Angelot-Delettre, Sabeha Biichle, Michael Seiler, Silvia Buonamici, Scott B. Lovitch, Abner Louissaint, Elizabeth A. Morgan, Fabrice Jardin, Pier Paolo Piccaluga, David M. Weinstock, Peter S. Hammerman, Henry Yang, Marina Konopleva, Naveen Pemmaraju, Francine Garnache-Ottou, Omar Abdel-Wahab, H. Phillip Koeffler, Andrew A. Lane
Summary: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia primarily occurring in males, and the mutations in X chromosome gene ZRSR2 are associated with impaired dendritic cell function and predisposition to leukemic transformation.
Article
Multidisciplinary Sciences
Aristeidis G. Telonis, Qin Yang, Hsuan-Ting Huang, Maria E. Figueroa
Summary: DNMT3A and IDH1/2 mutations together regulate the transcriptome and the epigenome in acute myeloid leukemia. The study found that genes with significant expression-methylation correlations are enriched in signaling and metabolic pathways. The common feature of these methylation-regulated genes is the density of MIR retrotransposons in their introns.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Koichi Takahashi, Tomoyuki Tanaka
Summary: Myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), are hematopoietic disorders characterized by genetic and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs). Recent advancements in clonal hematopoiesis research and single cell technologies have provided new insights into the developmental process of myeloid malignancies. This review explores the intricacies of clonal evolution in myeloid malignancies and its implications for the development of new diagnostic and therapeutic approaches.
Article
Multidisciplinary Sciences
Arda Durmaz, Carmelo Gurnari, Courtney E. Hershberger, Simona Pagliuca, Noah Daniels, Hassan Awada, Hussein Awada, Vera Adema, Minako Mori, Ben Ponvilawan, Yasuo Kubota, Tariq Kewan, Waled S. Bahaj, John Barnard, Jacob Scott, Richard A. Padgett, Torsten Haferlach, Jaroslaw P. Maciejewski, Valeria Visconte
Summary: RNA splicing dysfunctions are more widespread than believed and can't be solely attributed to splicing factor mutations in myeloid neoplasia. An integrative machine learning approach was applied to identify co-varying features in 1,258 MN cases and 63 normal controls, revealing 15 clusters based on mutations, gene expression, and RNA splicing. The combination of RNA splicing measurements and gene expression further distinguished features, identified similarities and differences in RNA splicing levels, and identified common pathways and expression signatures across the clusters.
Article
Hematology
Haley J. Abel, Karolyn A. Oetjen, Christopher A. Miller, Sai M. Ramakrishnan, Ryan B. Day, Nichole M. Helton, Catrina C. Fronick, Robert S. Fulton, Sharon E. Heath, Stefan P. Tarnawsky, Sridhar Nonavinkere Srivatsan, Eric J. Duncavage, Molly C. Schroeder, Jacqueline E. Payton, David H. Spencer, Matthew J. Walter, Peter Westervelt, John F. Dipersio, Timothy J. Ley, Daniel C. Link
Summary: TP53-mutated myeloid malignancies are associated with complex cytogenetics and extensive structural variants. The specific chromosome abnormalities are distinct to each cancer type, suggesting a dependence on the tissue of origin. NF1 and ETV6 mutations are highly enriched in TP53-mutated AML, and abnormal telomeric sequences were detected in the interstitial regions of chromosomes.
Article
Multidisciplinary Sciences
Abdul Rehman Khalil Shaikh, Ikram Ujjan, Muhammad Irfan, Arshi Naz, Tahir Shamsi, Muhammad Tariq Masood Khan, Muhammad Shakeel
Summary: The TET2 gene is involved in DNA methylation and epigenetic regulation in acute myeloid leukemia (AML). Studies in Pakistan found a high frequency of TET2 mutations in AML patients, with specific mutations correlated with AML subtypes and karyotypes.
Article
Hematology
Bin E. Li, Grace Y. Li, Wenqing Cai, Qian Zhu, Davide Seruggia, Yuko Fujiwara, Christopher R. Vakoc, Stuart H. Orkin
Summary: Through CRISPR/Cas9 screening and in vivo phenotypic readouts, we revealed a novel role for the Pbrm1 gene in leukemia progression and demonstrated that transcriptional control of interferon signaling influences the interaction between leukemia cells and the immune system.
Article
Medicine, Research & Experimental
Friedrich Stoelzel, Sarah E. Fordham, Devi Nandana, Wei-Yu Lin, Helen Blair, Claire Elstob, Hayden L. Bell, Brigitte Mohr, Leo Ruhnke, Desiree Kunadt, Claudia Dill, Daniel Allsop, Rachel Piddock, Emmanouela-Niki Soura, Catherine Park, Mohd Fadly, Thahira Rahman, Abrar Alharbi, Manja Wobus, Heidi Altmann, Christoph Roellig, Lisa Wagenfuehr, Gail L. Jones, Tobias Menne, Graham H. Jackson, Helen J. Marr, Jude Fitzgibbon, Kenan Onel, Manja Meggendorfer, Amber Robinson, Zuzanna Bziuk, Emily Bowes, Olaf Heidenreich, Torsten Haferlach, Sara Villar, Benat Ariceta, Rosa Ayala Diaz, Steven J. Altschuler, Lani F. Wu, Felipe Prosper, Pau Montesinos, Joaquin Martinez-Lopez, Martin Bornhaeuser, James M. Allan
Summary: Precision medicine is important in improving outcomes for cancer patients, and in this study, it was found that elderly patients with acute myeloid leukemia (AML) who had somatic biallelic TET2 mutations were resistant to certain chemotherapies but sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy. Experimental evidence showed that cells with biallelic TET2 mutations were more sensitive to 5'-Aza compared to cells with monoallelic mutations. This study suggests the potential use of hypomethylating agents as a treatment option for chemoresistant AML patients with biallelic TET2 mutations and highlights the importance of considering mutant allele dosage in precision medicine for cancer patients.
Article
Hematology
Yasuhito Nannya, Magnus Tobiasson, Shinya Sato, Elsa Bernard, Shigeki Ohtake, June Takeda, Maria Creignou, Lanying Zhao, Manabu Kusakabe, Yuhei Shibata, Nobuhiko Nakamura, Mizuki Watanabe, Nobuhiro Hiramoto, Yusuke Shiozawa, Yuichi Shiraishi, Hiroko Tanaka, Kenichi Yoshida, Nobuyuki Kakiuchi, Hideki Makishima, Masahiro Nakagawa, Kensuke Usuki, Mitsumasa Watanabe, Kazunori Imada, Hiroshi Handa, Masataka Taguchi, Toru Kiguchi, Kazuma Ohyashiki, Takayuki Ishikawa, Akifumi Takaori-Kondo, Hisashi Tsurumi, Senji Kasahara, Shigeru Chiba, Tomoki Naoe, Satoru Miyano, Elli Papaemanuil, Yasushi Miyazaki, Eva Hellstrom-Lindberg, Seishi Ogawa
Summary: The study aims to investigate the effect of gene mutations on hematological response and overall survival (OS) in patients with myelodysplastic syndrome (MDS)-related diseases, particularly focusing on posttreatment clone size. A total of 449 patients were enrolled and analyzed for gene mutations in pretreatment and posttreatment bone marrow samples to assess the impact of mutations and posttreatment clone size on treatment outcomes.
Article
Biochemistry & Molecular Biology
Giulia Biancon, Poorval Joshi, Joshua T. Zimmer, Torben Hunck, Yimeng Gao, Mark D. Lessard, Edward Courchaine, Andrew E. S. Barentine, Martin Machyna, Valentina Botti, Ashley Qin, Rana Gbyli, Amisha Patel, Yuanbin Song, Lea Kiefer, Gabriella Viero, Nils Neuenkirchen, Haifan Lin, Joerg Bewersdorf, Matthew D. Simon, Karla M. Neugebauer, Toma Tebaldi, Stephanie Halene
Summary: Splicing factor mutations, especially in U2AF1, are common drivers of myeloid malignancies, affecting the splicing process and leading to intron retention and exon exclusion. In addition, U2AF1 mutations directly influence the components of stress granules, which are involved in adaptive oncogenic strategies in cancer cells.
Article
Oncology
Rebeqa Gunnarsson, Sebastian Dilorenzo, Kristina B. Lundin-Strom, Linda Olsson, Andrea Biloglav, Henrik Lilljebjorn, Marianne Rissler, Per Wahlberg, Anders Lundmark, Anders Castor, Mikael Behrendtz, Thoas Fioretos, Kajsa Paulsson, Anders Isaksson, Bertil Johansson
Article
Oncology
James B. Studd, Minjun Yang, Zhenhua Li, Jayaram Vijayakrishnan, Yi Lu, Allen Eng-Juh Yeoh, Kajsa Paulsson, Richard S. Houlston
Article
Oncology
Ching-Hon Pui, Paola Rebora, Martin Schrappe, Andishe Attarbaschi, Andre Baruchel, Giuseppe Basso, Helene Cave, Sarah Elitzur, Katsuyoshi Koh, Hsi-Che Liu, Kajsa Paulsson, Rob Pieters, Lewis B. Silverman, Jan Stary, Ajay Vora, Allen Yeoh, Christine J. Harrison, Maria Grazia Valsecchi
JOURNAL OF CLINICAL ONCOLOGY
(2019)
Article
Oncology
Ola Forslund, Natsuki Sugiyama, Chengjun Wu, Naveen Ravi, Yuesheng Jin, Sabine Swoboda, Fredrik Andersson, Davit Bzhalava, Emilie Hultin, Kajsa Paulsson, Joakim Dillner, Stefan Schwartz, Johan Wennerberg, Lars Ekblad
Article
Oncology
Naveen Ravi, Minjun Yang, Sigurdur Gretarsson, Caroline Jansson, Nektaria Mylona, Saskia R. Sydow, Eleanor L. Woodward, Lars Ekblad, Johan Wennerberg, Kajsa Paulsson
Article
Multidisciplinary Sciences
Minjun Yang, Mattias Vesterlund, Ioannis Siavelis, Larissa H. Moura-Castro, Anders Castor, Thoas Fioretos, Rozbeh Jafari, Henrik Lilljebjorn, Duncan T. Odom, Linda Olsson, Naveen Ravi, Eleanor L. Woodward, Louise Harewood, Janne Lehtio, Kajsa Paulsson
NATURE COMMUNICATIONS
(2019)
Article
Otorhinolaryngology
Sigurdur Gretarsson, Alexander Nygren, Ann H. Rosendahl, Nektaria Mylona, Elisabeth Kjellen, Yuesheng Jin, Kajsa Paulsson, Ake Borg, Eva Brun, Jan Tennvall, Anders Bergenfelz, Lennart Greiff, Johan Wennerberg, Lars Ekblad
ACTA OTO-LARYNGOLOGICA
(2020)
Article
Hematology
Minjun Yang, Setareh Safavi, Eleanor L. Woodward, Nicolas Duployez, Linda Olsson-Arvidsson, Jonas Ungerback, Mikael Sigvardsson, Marketa Zaliova, Jan Zuna, Thoas Fioretos, Bertil Johansson, Karolin H. Nord, Kajsa Paulsson
Article
Oncology
Naveen Ravi, Minjun Yang, Nektaria Mylona, Johan Wennerberg, Kajsa Paulsson
Article
Oncology
Larissa H. Moura-Castro, Pablo Pena-Martinez, Anders Castor, Roman Galeev, Jonas Larsson, Marcus Jaras, Minjun Yang, Kajsa Paulsson
Summary: High hyperdiploid acute lymphoblastic leukemia (ALL) in children often displays defective sister chromatid cohesion, potentially due to low levels of cohesin or condensin, leading to a range of mild to very severe defects and increased chromosomal copy number heterogeneity. These abnormalities may contribute to clonal evolution in hyperdiploid pediatric ALL.
GENES CHROMOSOMES & CANCER
(2021)
Letter
Oncology
Rebeqa Gunnarsson, Minjun Yang, Linda Olsson-Arvidsson, Andrea Biloglav, Mikael Behrendtz, Anders Castor, Kajsa Paulsson, Bertil Johansson
Article
Oncology
Adam Stenman, Minjun Yang, Johan O. Paulsson, Jan Zedenius, Kajsa Paulsson, C. Christofer Juhlin
Summary: Anaplastic thyroid carcinoma is a deadly tumor with limited treatment options once it spreads. Research found genetic abnormalities in the patients that may respond to CDK inhibitors, as well as a phenomenon called kataegis, which could be therapeutically relevant.
Letter
Hematology
Agatheeswaran Subramaniam, Carl Sanden, Larissa Moura-Castro, Kristijonas Zemaitis, Ludwig Schmiderer, Aurelie Baudet, Alexandra Backstrom, Elin Arvidsson, Simon Hultmark, Natsumi Miharada, Mattias Magnusson, Kajsa Paulsson, Thoas Fioretos, Jonas Larsson
Letter
Oncology
Rebeqa Gunnarsson, Minjun Yang, Andrea Biloglav, Vladimir Lazarevic, Kajsa Paulsson, Bertil Johansson
Article
Multidisciplinary Sciences
Eleanor L. Woodward, Minjun Yang, Larissa H. Moura-Castro, Hilda van den Bos, Rebeqa Gunnarsson, Linda Olsson-Arvidsson, Diana C. J. Spierings, Anders Castor, Nicolas Duployez, Marketa Zaliova, Jan Zuna, Bertil Johansson, Floris Foijer, Kajsa Paulsson
Summary: This study reveals that the aneuploidies in high hyperdiploid acute lymphoblastic leukemia (HeH ALL) may originate early and follow a punctuated evolution process, using single-cell whole genome sequencing and in silico modeling.
NATURE COMMUNICATIONS
(2023)