Article
Medicine, Research & Experimental
Jianming Wang, Yang Liang, Yuefeng Qin, Guoyun Jiang, Yuhang Peng, Wenli Feng
Summary: This study uncovers that circCRKL is specifically expressed and regulates the expression level of BCR-ABL via decoying miR-877-5p in BCR-ABL(+) cells. The findings suggest that targeting circCRKL along with imatinib treatment could be a potential therapeutic strategy for CML patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Elena Vuelta, Jose L. Ordonez, David J. Sanz, Sandra Ballesteros, Jesus M. Hernandez-Rivas, Lucia Mendez-Sanchez, Manuel Sanchez-Martin, Ignacio Garcia-Tunon
Summary: This study demonstrates the therapeutic potential of a CRISPR-Trap system as a novel strategy for gene elimination in haematological neoplasms. The CRISPR-Trap efficiently interrupts the coding sequence of the oncogene and allows for the selection of edited cells. In vitro and in vivo experiments show the therapeutic benefit of this system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Roger S. Smith, Seesha R. Takagishi, David R. Amici, Kyle Metz, Sitaram Gayatri, Milad J. Alasady, Yaqi Wu, Sonia Brockway, Stephanie L. Taiberg, Natalia Khalatyan, Mikko Taipale, Sandro Santagata, Luke Whitesell, Susan Lindquist, Jeffrey N. Savas, Marc L. Mendillo
Summary: Heat shock factor 1 (HSF1) plays a crucial role in the heat shock response and tumorigenesis. This study reveals that HSF2 interacts with HSF1 in various types of cancer. HSF1 and HSF2 have similar chromatin occupancy and regulate a common set of genes, including HSPs and noncanonical transcriptional targets critical for supporting malignancy.
Article
Biotechnology & Applied Microbiology
Yuan Tan, Zhenglan Huang, Xin Wang, Hongdan Dai, Guoyun Jiang, Wenli Feng
Summary: This study identified a novel fusion circRNA (F-circBA1) originating from BCR-ABL, which is mainly localized in the cytoplasm and plays an oncogenic role in CML cells.
Article
Hematology
Xiaona You, Fabao Liu, Moritz Binder, Alexis Vedder, Terra Lasho, Zhi Wen, Xin Gao, Evan Flietner, Adhithi Rajagopalan, Yun Zhou, Christy Finke, Abhishek Mangaonkar, Ruiqi Liao, Guangyao Kong, Erik A. Ranheim, Nathalie Droin, Anthony M. Hunter, Sergey Nikolaev, Maria Balasis, Omar Abdel-Wahab, Ross L. Levine, Britta Will, Kalyan Vara Ganesh Nadiminti, David Yang, Klaus Geissler, Eric Solary, Wei Xu, Eric Padron, Mrinal M. Patnaik, Jing Zhang
Summary: Mutations in ASXL1 and NRAS genes are associated with poor prognosis in CMML. These mutations lead to dysregulation of MEK/ERK signaling, overexpression of immune checkpoint ligands, and exhaustion of T cells. Combination of targeted therapy and immunotherapy can improve these abnormalities and prolong the survival of AML patients.
Article
Oncology
Yan Yu, Zhao Zeng, Jundan Xie, Qiongyu Lu, Wenzhi Cai, Ruixi Zhang, Jinlan Pan, Yun Zhao, Aining Sun, Huiying Qiu, Suning Chen
Summary: The PAX5-UBE2D4 fusion gene identified in a case of Ph-positive mixed phenotype acute leukemia has partial oncogenic activity, promoting tumor growth and cell proliferation.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Anila Vadakumchery, Hemin Faraidun, Omar El Ayoubi, Issame Outaleb, Vera Schmid, Hend Abdelrasoul, Timm Amendt, Ahmad Khadour, Corinna Setz, Katharina Goehring, Karoline Lodd, Christoffer Hitzing, Alabbas Alkhatib, Mayas Bilal, Julian Benckendorff, Abdul Kader Al Shugri, Cord Herbert Brakebusch, Niklas Engels, Moumita Datta, Elias Hobeika, Ameera Alsadeq, Hassan Jumaa
Summary: The adaptor protein SLP65 controls the down-regulation of PI3K signaling in B cells by inducing the activity of small GTPase RHOA, which activates the negative regulator PTEN. RHOA plays a unique role in B cell generation and selection, and blocking its function offers potential for treating B cell malignancies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sara Zehtabcheh, Amir-Mohammad Yousefi, Majid Momeny, Davood Bashash
Summary: In this study, the combination of 10058-F4 and Imatinib showed synergistic effects in inhibiting the survival and proliferation of CML cells. The inhibition of c-Myc augmented the effectiveness of Imatinib by modulating the expression of genes related to cell cycle, apoptosis, autophagy, and proteasome. Further in-vivo examinations and clinical trials are necessary to validate these findings.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Gastroenterology & Hepatology
Alessandra Gentilini, Giulia Lori, Alessandra Caligiuri, Chiara Raggi, Giovanni Di Maira, Mirella Pastore, Benedetta Piombanti, Tiziano Lottini, Annarosa Arcangeli, Stefania Madiai, Nadia Navari, Jesus M. Banales, Sabina Di Matteo, Domenico Alvaro, Lea Duwe, Jesper B. Andersen, Alessandro Tubita, Ignazia Tusa, Luca Di Tommaso, Claudia Campani, Elisabetta Rovida, Fabio Marra
Summary: This study revealed the important role of ERK5 in the growth and migration of CCA cells, as well as its involvement in the protumorigenic crosstalk between the tumor and the microenvironment.
Article
Biochemistry & Molecular Biology
Kefeng Lin, Wenli Gao, Ning Chen, Shuyao Yang, Han Wang, Ran Wang, Fang Xie, Jiaqi Meng, Eric W. -F. Lam, Suyi Li, Wei Cheng, Puxiang Chen, Hongjin Wu, Jinsong Yan, Di Jin, Bilian Jin
Summary: Chronic inflammation and epigenetic reprogramming cooperate in glioblastoma, and targeting these processes can provide a powerful treatment strategy.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Oncology
Zhen Liu, Wenlong Zheng, Yuan Liu, Binghe Zhou, Yuqing Zhang, Fan Wang
Summary: The study showed that HSPA8 is overexpressed in imatinib-resistant CML cells and its ablation can inhibit cell proliferation, induce autophagy, and enhance the anti-tumor activity of imatinib. These findings reveal the role of HSPA8 in IR-CML and suggest its potential as a target for treatment.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Shohei Kawakami, Mitsuyo Tsuma-Kaneko, Masakazu Sawanobori, Tomoko Uno, Yoshihiko Nakamura, Hideyuki Matsuzawa, Rikio Suzuki, Makoto Onizuka, Takashi Yahata, Kazuhito Naka, Kiyoshi Ando, Hiroshi Kawada
Summary: This study found that pterostilbene has significant antileukemic effects and can induce apoptosis in leukemic cells, especially in those with the BCR/ABL fusion gene. Pterostilbene also downregulated the BCR/ABL fusion protein levels and suppressed AKT and NF-kappa B activation in BCR/ABL(+) leukemic cells.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Puneet Agarwal, Hui Li, Kwangmin Choi, Kathleen Hueneman, Jianbo He, Robert S. Welner, Daniel T. Starczynowski, Ravi Bhatia
Summary: Chronic myeloid leukemia is maintained and propagated by leukemia stem cells (LSCs) in bone marrow through tumor necrosis factor alpha-mediated CXCL1-CXCR2 signaling. Inhibition of CXCR2 effectively depletes CML LSCs and can enhance LSC targeting when combined with tyrosine kinase inhibitors (TKIs). TNF-alpha-induced alterations in CML BM stromal niches support LSC maintenance and growth.
Article
Hematology
Lauren M. Brown, Soroor Hediyeh-Zadeh, Teresa Sadras, Hannah Huckstep, Jarrod J. Sandow, Ray C. Bartolo, Hansen J. Kosasih, Nadia M. Davidson, Breon Schmidt, Stefan Bjelosevic, Ricky Johnstone, Andrew Webb, Seong L. Khaw, Alicia Oshlack, Melissa J. Davis, Paul G. Ekert
Summary: This study identified a rare SFPQ-ABL1 fusion gene that plays a crucial role in cellular transformation in Ph-like ALL. Unlike other ABL1 fusion genes, SFPQ-ABL1 exhibits differences in subcellular localization, proliferative capacity, and activation of cellular pathways. These findings highlight the significance of fusion partners in mediating the function of ABL1 fusion genes.
Article
Chemistry, Medicinal
Xu-Xiu Lu, Yao-Yao Jiang, Yan-Wei Wu, Guang-Ying Chen, Chang-Lun Shao, Yu-Cheng Gu, Ming Liu, Mei-Yan Wei
Summary: Brefeldin A, a natural compound with potent cytotoxic activity, was synthesized from the medicinal mangrove Acanthus ilicifolius by a marine fungus Penicillium sp. In this study, a series of ester derivatives were designed and synthesized, and their cytotoxic activities against human chronic myelogenous leukemia K562 cells were evaluated. Among them, the monoester derivative 7 exhibited the strongest inhibitory effect on cell proliferation, inducing cell cycle arrest and promoting cell apoptosis. Furthermore, molecular modeling suggested that compound 7 could effectively bind to the target site. These findings highlight the potential of compound 7 as a promising antileukemia agent or lead compound for further exploration.
Article
Hematology
Priyanka Mehta, Nick Telford, Chris Wragg, Richard Dillon, Sylvie Freeman, Damian Finnegan, Angela Hamblin, Mhairi Copland, Steve Knapper
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Steffen Koschmieder, Susanne Isfort, Dominik Wolf, Florian H. Heidel, Andreas Hochhaus, Philippe Schafhausen, Martin Griesshammer, Denise Wolleschak, Uwe Platzbecker, Konstanze Doehner, Philipp J. Jost, Stefani Parmentier, Markus Schaich, Nikolas von Bubnoff, Frank Stegelmann, Angela Maurer, Martina Crysandt, Deniz Gezer, Maike Kortmann, Jeremy Franklin, Julia Frank, Martin Hellmich, Tim H. Bruemmendorf
Summary: This study found that treatment with ruxolitinib is effective, well-tolerated, and efficient for previously untreated patients with polycythemia vera, with significant reduction in symptoms and improvement in hematological parameters.
ANNALS OF HEMATOLOGY
(2023)
Article
Biology
George B. Garside, Madeline Sandoval, Slobodan Beronja, K. Lenhard Rudolph
Summary: This study developed a novel technique for in vivo targeting of intestinal stem cells in the unperturbed intestinal epithelium across different regions of the intestine. This method enables in vivo somatic gene editing and genetic screening, which can speed up discoveries and mechanistic understanding of genetic pathways controlling the biology of the intestinal epithelium.
Review
Medical Laboratory Technology
Florent J. L. A. Vanstapel, Matthias Orth, Thomas Streichert, Ettore D. Capoluongo, Wytze P. Oosterhuis, Hikmet Can Cubukcu, Francisco A. Bernabeu-Andreu, Marc Thelen, Leo H. J. Jacobs, Solveig Linko, Harjit Pal Bhattoa, Patrick M. M. Bossuyt, Pika Mesko Brguljan, Guilaine Boursier, Christa M. Cobbaert, Michael Neumaier
Summary: The EU In-Vitro Diagnostic Device Regulation (IVDR) aims to ensure transparent validation of diagnostic devices, traceability of results, and post-market surveillance. Laboratory-developed tests (LDTs) may be used in the absence of suitable commercial devices. The implementation of IVDR may lead to the need for urgent replacement of commercial tests with LDTs, and the workload will depend on various factors.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Francesca Ferraro, Anja Steinle, Harini Narasimhan, Andreas Bleilevens, Paula-Marie Stolzenberg, Till Braunschweig, Elmar Stickeler, Jochen Maurer
Summary: Breast cancer stem cells (BCSCs) play a crucial role in tumor recurrence and therapy resistance. Researchers have successfully established primary BCSC cultures from triple-negative breast cancer (TNBC) patients, providing an excellent model for studying breast cancer treatment options. IRAK2 downregulation shows promising results in inhibiting the aggressive growth and pathways involved in TNBC progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Chadi Barakat, Marcel Aach, Andreas Schuppert, Sigurour Brynjolfsson, Sebastian Fritsch, Morris Riedel
Summary: The COVID-19 pandemic has highlighted the importance of quick diagnosis tools in healthcare. This paper presents a data analysis and machine learning platform that utilizes high-performance computing infrastructure for medical diagnosis support applications. The platform improves the performance of a deep learning model through large-scale hyperparameter optimization and demonstrates higher accuracy in disease detection. It also shows a decrease in training time with increased resources, but identifies a cut-off point where communication overhead affects performance.
Article
Biochemistry & Molecular Biology
Marcelo A. S. de Toledo, Xuhuang Fu, Tiago Maie, Eva M. Buhl, Katrin Goetz, Susanne Schmitz, Anne Kaiser, Peter Boor, Till Braunschweig, Nicolas Chatain, Ivan G. Costa, Tim H. Bruemmendorf, Steffen Koschmieder, Martin Zenke
Summary: In this study, human induced pluripotent stem cells were differentiated into mast cells, which exhibited characteristics of systemic mastocytosis disease. These cells can be used for disease modeling and drug screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Oncology
Kirsi Manz, Jeanette Bahr, Till Ittermann, Konstanze Doehner, Steffen Koschmieder, Tim H. H. Bruemmendorf, Martin Griesshammer, Matthias Nauck, Henry Voelzke, Florian H. H. Heidel
Letter
Oncology
Yulin Chen, Susanne Moebius, Konstantin Riege, Steve Hoffmann, Andreas Hochhaus, Thomas Ernst, Karl Lenhard Rudolph
Article
Cell Biology
Axel Dievernich, Johannes Stegmaier, Pascal Achenbach, Svetlana Warkentin, Till Braunschweig, Ulf Peter Neumann, Uwe Klinge
Summary: Liver cancer, particularly hepatocellular carcinoma (HCC), is a common and deadly form of cancer worldwide. Numerous studies have examined the impact of immune infiltrates on cancer patient prognosis, but accurately delineating the cancer area has been challenging due to heterogeneity and operator variability. However, advancements in multiplex analyses and machine learning techniques offer potential for objective identification of cancer areas and analysis of prognostic immune parameters.
Article
Medicine, General & Internal
Chadi S. Barakat, Konstantin Sharafutdinov, Josefine Busch, Sina Saffaran, Declan G. Bates, Jonathan G. Hardman, Andreas Schuppert, Sigurdur Brynjolfsson, Sebastian Fritsch, Morris Riedel
Summary: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition that gradually reduces lung function in Intensive Care Unit patients. Diagnosis and treatment have been challenging due to its heterogeneity, but continuous research has led to the development of modeling tools and diagnosis guidelines. This paper presents the development of a deep learning-based surrogate model for ARDS onset in virtual patients, using machine learning techniques and high-performance computing. The lightweight models developed show comparable accuracy to the original simulator, making them a potential support system in clinical routines.
Article
Hematology
Steffen Koschmieder, Susanne Isfort, Clemens Schulte, Lutz Jacobasch, Thomas Geer, Marcel Reiser, Michael Koenigsmann, Bernhard Heinrich, Jurgen Wehmeyer, Eyck von der Heyde, Hans Tesch, Benedikt Groeschl, Petra Bachhuber, Susanne Grosser, Heike L. Pahl
Summary: This study provides evidence for the safety and efficacy of ruxolitinib in elderly JAKi-naive patients with myelofibrosis in a real-world setting. The results show that ruxolitinib treatment leads to a reduction in spleen size and significant improvement in symptoms. Common adverse events include anemia and thrombocytopenia. Overall, ruxolitinib is a safe and effective treatment option for JAKi-naive patients with myelofibrosis.
ANNALS OF HEMATOLOGY
(2023)
Article
Medical Laboratory Technology
Wouter H. G. Hubens, Tiago Maie, Matthis Schnitker, Ledio Bocova, Deepika Puri, Martina Wessiepe, Jan Kramer, Lothar Rink, Steffen Koschmieder, Ivan G. Costa, Wolfgang Wagner
Summary: Cell-type specific DNA methylation can be used to accurately count different leukocyte subsets in blood. In this study, the authors developed targeted DNAm assays and used digital droplet PCR to measure DNAm levels in venous blood and dried blood samples. The results showed good correlations between epigenetic estimates and conventional cell counting methods, and dried blood samples facilitated self-sampling for easier testing accessibility.
CLINICAL CHEMISTRY
(2023)
Editorial Material
Hematology
Madeline J. Caduc, Steffen Koschmieder
Article
Hematology
Mhairi Copland, Cono Ariti, Ian F. Thomas, Laura Upton, Mia Sydenham, Priyanka Mehta, Shahid Islam, Lars Kjeldsen, Alan K. Burnett, Robert K. Hills, Nigel Russell, Mike Dennis
Summary: Improving outcomes for older patients with acute myeloid leukaemia is still an unmet need. In this study, we evaluated the effectiveness of lenalidomide in combination with low-dose cytosine arabinoside compared to low-dose cytosine arabinoside alone in unfit patients aged over 60. The combination therapy showed a higher overall response rate, but there was no difference in overall survival between the two arms.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)