Article
Medicine, Research & Experimental
Xue-Ping Li, Wei-Na Zhang, Jia-Ying Mao, Bai-Tian Zhao, Lu Jiang, Yan Gao
Summary: In this study, we constructed a CD34(+)CD117(dim) population signature model for predicting clinical outcome of AML patients using gene expression and RNA-seq data. The high-risk group exhibited worse overall survival and had activated immune signaling pathways. This model may serve as a valuable tool for stratifying AML patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Claudia Banescu, Florin Tripon, Carmen Muntean
Summary: Myelodysplastic neoplasm (MDS) is a diverse group of myeloid disorders that arise from hematopoietic stem cells and can progress to clonal hematopoiesis. MDS is characterized by an increased risk of transforming into acute myeloid leukemia (AML). Advances in next-generation sequencing (NGS) have revealed numerous recurrent mutations in genes such as FLT3, NPM1, DNMT3A, TP53, NRAS, and RUNX1. The acquisition order of gene mutations during MDS progression to leukemia is non-random and has prognostic significance. Understanding the molecular events behind MDS transformation to AML has paved the way for targeted and personalized treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Benedicte Sjo Tislevoll, Monica Hellesoy, Oda Helen Eck Fagerholt, Stein-Erik Gullaksen, Aashish Srivastava, Even Birkeland, Dimitrios Kleftogiannis, Pilar Ayuda-Duran, Laure Piechaczyk, Dagim Shiferaw Tadele, Jorn Skavland, Baliakas Panagiotis, Randi Hovland, Vibeke Andresen, Ole Morten Seternes, Tor Henrik Anderson Tvedt, Nima Aghaeepour, Sonia Gavasso, Kimmo Porkka, Inge Jonassen, Yngvar Floisand, Jorrit Enserink, Nello Blaser, Bjorn Tore Gjertsen
Summary: In this study, the initial signaling response to standard induction chemotherapy in 32 acute myeloid leukemia (AML) patients was investigated using 36-dimensional mass cytometry. The reduction of extracellular-signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the myeloid cell compartment 24 h post-chemotherapy was found to be a significant predictor of patient 5-year overall survival in this cohort. This study demonstrates the value of mass cytometry in early response evaluation in AML and highlights the potential of functional signaling analyses in precision oncology diagnostics.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Sargam Kapoor, Grace Champion, Aparna Basu, Anu Mariampillai, Matthew J. Olnes
Summary: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow with poor prognosis. Recent advancements in immune therapies, including immune suppressive therapy and novel treatments like monoclonal antibodies and cellular therapeutics, have shown promise in treating these diseases.
Article
Multidisciplinary Sciences
Adrian Mosquera Orgueira, Andres Peleteiro Raindo, Miguel Cid Lopez, Beatriz Antelo Rodriguez, Jose Angel Diaz Arias, Roi Ferreiro Ferro, Natalia Alonso Vence, Angeles Bendana Lopez, Aitor Abuin Blanco, Laura Bao Perez, Paula Melero Valentin, Marta Sonia Gonzalez Perez, Claudio Cerchione, Giovanni Martinelli, Pau Montesinos Fernandez, Manuel Mateo Perez Encinas, Jose Luis Bello Lopez
Summary: A FLT3 mutation-like gene expression pattern was identified in wild-type FLT3 AML, highly enriched in NPM1 and DNMT3A mutations. Further analysis is needed to explore the predictive role of this biomarker in wild-type FLT3 patients treated with FLT3 inhibitors.
Article
Oncology
Howard Lopes Ribeiro Junior, Paola Gyuliane Goncalves, Daniel Antunes Moreno, Joao Vitor Caetano Goes, Roberta Taiane Germano de Oliveira, Carlos Victor Montefusco-Pereira, Tatiana Takahasi Komoto, Ronald Feitosa Pinheiro
Summary: Through transcriptome analysis of CD34(+) HSC and PBMC from MDS patients, we identified differential gene expression patterns between these two cell types, which may serve as pathogenic biomarkers for MDS. We also observed a certain similarity in the activated pathways in both cell types. These findings have clinical significance for the diagnosis and treatment of MDS.
Article
Oncology
Betul Oran, Rima M. Saliba, Rohtesh S. Mehta, Amin M. Alousi, David Marin, Ben C. Valdez, Julianne Chen, Qaiser Bashir, Stefan O. Ciurea, Amanda L. Olson, Chitra Hosing, Partow Kebriaei, Katy Rezvani, Elizabeth J. Shpall, Richard E. Champlin, Borje S. Andersson, Uday R. Popat
Summary: Fractionated busulfan treatment in patients with AML or myelodysplastic syndrome improves progression-free survival and overall survival without increasing nonrelapse mortality, compared to nonfractionated lower dose regimens.
Review
Immunology
Sarah Weber, Anastasia Parmon, Nina Kurrle, Frank Schnuetgen, Hubert Serve
Summary: MDS and AML patients often experience systemic iron overload issues, iron is closely associated with the pathogenesis and potential treatment strategies of the diseases, imbalances in iron homeostasis may lead to various cell death.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Vlad Andrei Cianga, Lydia Campos Catafal, Petru Cianga, Mariana Pavel Tanasa, Mohamad Cherry, Phillipe Collet, Emmanuelle Tavernier, Denis Guyotat, Cristina Rusu, Carmen Mariana Aanei
Summary: The study investigated NK cell maturation in bone marrow under different conditions and found impaired NK cell antitumor response and phenotypic shift in MDS and AML settings. The results suggest immune response failure during myeloid malignancy pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Na Man, Gloria Mas, Daniel L. Karl, Jun Sun, Fan Liu, Qin Yang, Miguel Torres-Martin, Hidehiro Itonaga, Concepcion Martinez, Shi Chen, Ye Xu, Stephanie Duffort, Pierre-Jacques Hamard, Chuan Chen, Beth E. Zucconi, Luisa Cimmino, Feng-Chun Yang, Mingjiang Xu, Philip A. Cole, Maria E. Figueroa, Stephen D. Nimer
Summary: This study identified a tumor suppressor role of the acetyltransferase p300 in MDS, with loss of p300 enhancing HSPC proliferation and self-renewal, ultimately increasing leukemogenicity. Mechanistically, loss of p300 altered gene expression and promoted leukemia development, while activating p300 activity countered these effects. This suggests a potential therapeutic application of p300 activators in treating MDS with TET2 mutations.
Article
Medicine, Research & Experimental
Yang Mei, Kehan Ren, Yijie Liu, Annabel Ma, Zongjun Xia, Xu Han, Ermin Li, Hamza Tariq, Haiyan Bao, Xinshu Xie, Cheng Zou, Dingxiao Zhang, Zhaofeng Li, Lili Dong, Amit Verma, Xinyan Lu, Yasmin Abaza, Jessica K. Altman, Madina Sukhanova, Jing Yang, Peng Ji
Summary: This study reveals that age-related MDS can transform into AML, and the cytokine IL-6 plays a significant role in this transformation. By studying a double knockout mouse model and high-risk MDS patients, blocking IL-6 signaling was found to significantly ameliorate AML progression, indicating the clinical significance of targeting IL-6 signaling in treating high-risk MDS.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Biochemistry & Molecular Biology
Thomas Cluzeau, Michael Loschi, Pierre Fenaux, Rami Komrokji, David A. Sallman
Summary: This article reviews the progress in targeting TP53 mutated myelodysplastic syndromes and acute myeloid leukemia, focusing on the use of active agents and future treatment directions. It emphasizes the importance of understanding the clinical characteristics of the disease and the impact of TP53 mutant burden on patient clinical trajectory.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Yasmin Abaza, Amer M. Zeidan
Summary: Immune checkpoint inhibitors have had a significant impact on the treatment of solid tumors, but there has been limited progress in myeloid malignancies. The low mutational burden of acute myeloid leukemia is a potential reason for the lack of response to T-cell harnessing ICIs. Targeting agents, such as magrolimab and sabatolimab, in combination with other drugs, have shown promising activity in early clinical trials.
Article
Oncology
Shyam A. Patel, Maxwell R. Lloyd, Jan Cerny, Qiming Shi, Karl Simin, Asiri Ediriwickrema, Lloyd Hutchinson, Patricia M. Miron, Anne W. Higgins, Muthalagu Ramanathan, Jonathan M. Gerber
Summary: TP53 disruptions are associated with mutations in epigenetic regulators, spliceosome machinery, and cohesin complex, but show low co-occurrence with mutations in proliferative signaling genes. High mutant TP53 gene dosage predicts low durability of remission. Treatment with hypomethylating agents can improve patient survival rates.
LEUKEMIA & LYMPHOMA
(2021)
Article
Genetics & Heredity
Mercy Gatua, Mohsen Navari, Matilda Ong'ondi, Noel Onyango, Serah Kaggia, Emily Rogena, Giuseppe Visani, Nicholas A. Abinya, Pier Paolo Piccaluga
Summary: This study describes the cytogenetic and molecular abnormalities of AML patients in Kenya, highlighting the limitations of AML diagnostics and treatment and confirming the relevance of advanced next generation sequencing technologies in AML characterization.
FRONTIERS IN GENETICS
(2022)
Letter
Hematology
Zuzana Chyra, Tereza Sevikova, Petr Vojta, Janka Puterova, Lucie Brozova, Katerina Growkova, Jana Filipova, Martina Zatopkova, Sebastian Grosicki, Agnieszka Barchnicka, Wieslaw Wiktor-Jedrzejczak, Anna Waszczuk-Gajda, Alexandra Jungova, Aneta Mikulasova, Marian Hajduch, Martin Mokrejs, Ludek Pour, Martin Stork, Lubica Harvanova, Martin Mistrik, Gabor Mikala, Pawel Robak, Anna Czyz, Jakub Debski, Lidia Usnarska-Zubkiewicz, Artur Jurczyszyn, Lukas Stejskal, Gareth Morgan, Fedor Kryukov, Eva Budinska, Michal Simicek, Tomas Jelinek, Matous Hrdinka, Roman Hajek
Article
Environmental Sciences
Qing Hua, Ondrej Adamovsky, Hana Vespalcova, Jonna Boyda, Jordan T. Schmidt, Marianne Kozuch, Serena L. M. Craft, Pamela E. Ginn, Stanislav Smatana, Eva Budinska, Maria Persico, Joseph H. Bisesi, Christopher J. Martyniuk
Summary: The study showed that environmentally-relevant doses of dieldrin did not significantly affect the gastrointestinal morphology and body weight of zebrafish, but altered the microbiome composition, including reductions in Firmicutes, Clostridia, and Betaproteobacteria. The predicted metabolic turnover analysis indicated potential impacts on bacterial heme biosynthesis and selenium metabolism pathways in the fish gastrointestinal system. Further research is needed to fully understand the long-term consequences of dietary exposure to dieldrin on microbiota composition.
ENVIRONMENTAL POLLUTION
(2021)
Article
Chemistry, Medicinal
Hana Votavova, Zuzana Urbanova, David Kundrat, Michaela Dostalova Merkerova, Martin Vostry, Monika Hruba, Jaroslav Cermak, Monika Belickova
Summary: DFX improves hematopoiesis in anemic myelodysplastic syndrome patients by modulating immune response, suppressing negative regulators of blood cell differentiation, and upregulating heme metabolism.
Correction
Biochemistry & Molecular Biology
Elsa Bernard, Yasuhito Nannya, Robert P. Hasserjian, Sean M. Devlin, Heinz Tuechler, Juan S. Medina-Martinez, Tetsuichi Yoshizato, Yusuke Shiozawa, Ryunosuke Saiki, Luca Malcovati, Max F. Levine, Juan E. Arango, Yangyu Zhou, Francesc Sole, Catherine A. Cargo, Detlef Haase, Maria Creignou, Ulrich Germing, Yanming Zhang, Gunes Gundem, Araxe Sarian, Arjan A. van de Loosdrecht, Martin Jadersten, Magnus Tobiasson, Olivier Kosmider, Matilde Y. Follo, Felicitas Thol, Ronald F. Pinheiro, Valeria Santini, Ioannis Kotsianidis, Jacqueline Boultwood, Fabio P. S. Santos, Julie Schanz, Senji Kasahara, Takayuki Ishikawa, Hisashi Tsurumi, Akifumi Takaori-Kondo, Toru Kiguchi, Chantana Polprasert, John M. Bennett, Virginia M. Klimek, Michael R. Savona, Monika Belickova, Christina Ganster, Laura Palomo, Guillermo Sanz, Lionel Ades, Matteo Giovanni Della Porta, Alexandra G. Smith, Yesenia Werner, Minal Patel, Agnes Viale, Katelynd Vanness, Donna S. Neuberg, Kristen E. Stevenson, Kamal Menghrajani, Kelly L. Bolton, Pierre Fenaux, Andrea Pellagatti, Uwe Platzbecker, Michael Heuser, Peter Valent, Shigeru Chiba, Yasushi Miyazaki, Carlo Finelli, Maria Teresa Voso, Lee-Yung Shih, Michaela Fontenay, Joop H. Jansen, Jose Cervera, Yoshiko Atsuta, Norbert Gattermann, Benjamin L. Ebert, Rafael Bejar, Peter L. Greenberg, Mario Cazzola, Eva Hellstrom-Lindberg, Seishi Ogawa, Elli Papaemmanuil
Correction
Biochemistry & Molecular Biology
Elsa Bernard, Yasuhito Nannya, Robert P. Hasserjian, Sean M. Devlin, Heinz Tuechler, Juan S. Medina-Martinez, Tetsuichi Yoshizato, Yusuke Shiozawa, Ryunosuke Saiki, Luca Malcovati, Max F. Levine, Juan E. Arango, Yangyu Zhou, Francesc Sole, Catherine A. Cargo, Detlef Haase, Maria Creignou, Ulrich Germing, Yanming Zhang, Gunes Gundem, Araxe Sarian, Arjan A. van de Loosdrecht, Martin Jadersten, Magnus Tobiasson, Olivier Kosmider, Matilde Y. Follo, Felicitas Thol, Ronald F. Pinheiro, Valeria Santini, Ioannis Kotsianidis, Jacqueline Boultwood, Fabio P. S. Santos, Julie Schanz, Senji Kasahara, Takayuki Ishikawa, Hisashi Tsurumi, Akifumi Takaori-Kondo, Toru Kiguchi, Chantana Polprasert, John M. Bennett, Virginia M. Klimek, Michael R. Savona, Monika Belickova, Christina Ganster, Laura Palomo, Guillermo Sanz, Lionel Ades, Matteo Giovanni Della Porta, Alexandra G. Smith, Yesenia Werner, Minal Patel, Agnes Viale, Katelynd Vanness, Donna S. Neuberg, Kristen E. Stevenson, Kamal Menghrajani, Kelly L. Bolton, Pierre Fenaux, Andrea Pellagatti, Uwe Platzbecker, Michael Heuser, Peter Valent, Shigeru Chiba, Yasushi Miyazaki, Carlo Finelli, Maria Teresa Voso, Lee-Yung Shih, Michaela Fontenay, Joop H. Jansen, Jose Cervera, Yoshiko Atsuta, Norbert Gattermann, Benjamin L. Ebert, Rafael Bejar, Peter L. Greenberg, Mario Cazzola, Eva Hellstrom-Lindberg, Seishi Ogawa, Elli Papaemmanuil
Article
Oncology
Pavla Koralkova, Monika Belickova, David Kundrat, Michaela Dostalova Merkerova, Zdenek Krejcik, Katarina Szikszai, Monika Kaisrlikova, Jitka Vesela, Pavla Vyhlidalova, Jan Stetka, Alzbeta Hlavackova, Jiri Suttnar, Patrik Flodr, Jan Stritesky, Anna Jonasova, Jaroslav Cermak, Vladimir Divoky
Summary: The study sheds light on the molecular network complexity underlying response/resistance to hypomethylating agents in MDS and AML-MRC, suggesting that the metabolic status and transcriptional characteristics of CD34(+) cells may be pivotal factors in predicting patient responses.
Meeting Abstract
Oncology
V. Popovici, T. Ivkovic, M. Hrivnakova, R. Nenutil, L. Zdrazilova-Dubska, M. Nemecek, O. Slaby, B. Bencsikova, E. Budinska
ANNALS OF ONCOLOGY
(2021)
Article
Psychiatry
Ibrahim A. Akkouh, Hana Hribkova, Marta Grabiec, Eva Budinska, Attila Szabo, Tomas Kasparek, Ole A. Andreassen, Yuh-Man Sun, Srdjan Djurovic
Summary: Using hiPSC technology, researchers derived a subtype of astrocytes from healthy individuals and schizophrenia patients, finding a distinct gene expression signature specific to schizophrenia. Astrocyte diversity may potentially modulate schizophrenia pathophysiology and drug response, warranting further investigation.
SCHIZOPHRENIA BULLETIN
(2022)
Article
Microbiology
Anne-Christine Aust, Eliska Benesova, Veronika Vidova, Katerina Coufalikova, Sona Smetanova, Ivo Borek, Petr Janku, Eva Budinska, Jana Klanova, Vojtech Thon, Zdenek Spacil
Summary: National screening programs use dried blood samples to detect metabolic disorders or aberrant protein functions that may not be clinically evident in newborns, with a focus on gut microbiota metabolites and immunological acute-phase proteins. The delivery method (vaginal or cesarean section) plays a significant role in shaping microbial colonization and influencing the immune system's response and mucosal homeostasis in neonates. The study identified microbial xenobiotic receptors ligands in neonatal blood samples on the second day of life, indicating the potential importance of the human gut microbiota in maintaining immune system homeostasis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Oncology
Barbora Zwinsova, Vyacheslav A. Petrov, Martina Hrivnakova, Stanislav Smatana, Lenka Micenkova, Natalie Kazdova, Vlad Popovici, Roman Hrstka, Roman Sefr, Beatrix Bencsikova, Lenka Zdrazilova-Dubska, Veronika Brychtova, Rudolf Nenutil, Petra Videnska, Eva Budinska
Summary: This study suggests that dysbiosis of the gut microbiome plays a role in the heterogeneity of colorectal cancer, affecting its phenotypic, prognostic, and treatment response aspects. The dominance of oral pathogenic bacteria in tumour mucosa of CRC patients was observed, while changes in stool microbiome were associated with clinical parameters such as lymph node involvement and synchronous metastases. The study identified new associations between microorganisms and CRC, providing insights for potential new treatments and biomarkers.
Article
Nutrition & Dietetics
Magdalena Prochazkova, Eva Budinska, Marek Kuzma, Helena Pelantova, Jaromir Hradecky, Marie Heczkova, Nikola Daskova, Miriam Bratova, Istvan Modos, Petra Videnska, Petra Splichalova, Solomon A. Sowah, Maria Kralova, Marina Henikova, Eliska Selinger, Krystof Klima, Karel Chalupsky, Radislav Sedlacek, Rikard Landberg, Tilman Kuehn, Jan Gojda, Monika Cahova
Summary: There are differences in microbiome composition and function related to metabolic health between individuals adhering to a vegan vs. omnivore diet. Vegans tend to have better glucose and lipid homeostasis profiles. The metabolomes of vegans and omnivores show significant differences, with vegans having lower abundance of potentially harmful metabolites and higher occurrence of potentially beneficial ones.
FRONTIERS IN NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Christopher J. Martyniuk, Amanda N. Buerger, Hana Vespalcova, Barbora Rudzanova, Shahadur R. Sohag, Amy T. Hanlon, Pamela E. Ginn, Serena L. Craft, Sona Smetanova, Eva Budinska, Joseph H. Bisesi, Ondrej Adamovsky
Summary: The study investigates the differences in microbial composition and diversity between male and female zebrafish. No significant differences were found in gut microbial diversity and predicted functional composition between the two sexes. However, there were differences in the abundance of certain bacterial families and genera. Transcriptome analysis revealed unique differentially expressed transcripts in the gastrointestinal tissue and differences in gene networks related to immune function and lipid metabolism between males and females.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS
(2022)
Article
Oncology
Monika Kaisrlikova, Jitka Vesela, David Kundrat, Hana Votavova, Michaela Dostalova Merkerova, Zdenek Krejcik, Vladimir Divoky, Marek Jedlicka, Jan Fric, Jiri Klema, Dana Mikulenkova, Marketa Stastna Markova, Marie Lauermannova, Jolana Mertova, Jacqueline Soukupova Maaloufova, Anna Jonasova, Jaroslav Cermak, Monika Belickova
Summary: This study found that the RUNX1 mutation is the main predictor of rapid progression in LR-MDS patients. Comparison of gene expression profiles between patients with and without RUNX1 mutations suggests that RUNX1 mutations may trigger malignant transformation. Dysregulation of DDR and cellular senescence was also observed. Additionally, the expression profiles of RUNX1-mutated LR-MDS resemble those of higher-risk MDS.
Article
Gastroenterology & Hepatology
Barbara Pardini, Giulio Ferrero, Sonia Tarallo, Gaetano Gallo, Antonio Francavilla, Nicola Licheri, Mario Trompetto, Giuseppe Clerico, Carlo Senore, Sergio Peyre, Veronika Vymetalkova, Ludmila Vodickova, Vaclav Liska, Ondrej Vycital, Miroslav Levy, Peter Macinga, Tomas Hucl, Eva Budinska, Pavel Vodicka, Francesca Cordero, Alessio Naccarati
Summary: This study comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive colorectal cancer (CRC) diagnosis. A 5-miRNA signature accurately distinguished patients from control individuals and showed good correlation with tissue miRNA profiles and fecal profiles of different gastrointestinal diseases. These findings have the potential to improve noninvasive diagnosis and screening strategies for CRC.
Article
Microbiology
Eva Konecna, Petra Videnska, Lucie Buresova, Milan Urik, Sona Smetanova, Stanislav Smatana, Roman Prokes, Barbara Lanickova, Eva Budinska, Jana Klanova, Petra Borilova Linhartova
Summary: This pilot study aimed to investigate the changes in human nasopharyngeal bacteriome after short-term exposure to indoor environments. Nasopharyngeal swabs and indoor dust samples were collected from 22 participants, and 16S rRNA sequencing analysis showed that short-term exposure to indoor environments can result in the enrichment of the nasopharynx with bacterial DNA from indoor dust. However, the bacterial composition varies by the indoor workplace environment.
