Article
Oncology
Husheng Ding, Nicole D. Vincelette, Cordelia D. McGehee, Mira A. Kohorst, Brian D. Koh, Annapoorna Venkatachalam, X. Wei Meng, Paula A. Schneider, Karen S. Flatten, Kevin L. Peterson, Cristina Correia, Sun-Hee Lee, Mrinal Patnaik, Jonathan A. Webster, Gabriel Ghiaur, B. Douglas Smith, Judith E. Karp, Keith W. Pratz, Hu Li, Larry M. Karnitz, Scott H. Kaufmann
Summary: This study shows that replication checkpoint inhibitors can kill AML cells through a pathway involving AP1-mediated TNF gene activation and subsequent TP53-independent, TNF alpha-induced apoptosis, which could have potential clinical implications.
Article
Cell Biology
Fanting Zeng, Yuhang Peng, Yuefeng Qin, Jianming Wang, Guoyun Jiang, Wenli Feng, Ying Yuan
Summary: Wee1 plays a crucial role in the treatment of CML by regulating DNA damage repair. Inhibiting Wee1 can improve the sensitivity to Imatinib and inhibit cancer cell proliferation.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Fieke W. Hoff, Ti'ara L. Griffen, Brandon D. Brown, Terzah M. Horton, Jan Burger, William Wierda, Stefan E. Hubner, Yihua Qiu, Steven M. Kornblau
Summary: DNA damage response (DNADR) recognition and repair (DDR) pathways play a role in carcinogenesis and therapy responsiveness in leukemia. In this study, we analyzed the protein expression levels of 16 DNADR and DDR proteins in acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia (T-ALL), and chronic lymphocytic leukemia (CLL) cases. Findings showed distinct protein expression clusters across the leukemias, with individual protein expression differing by disease and age. The clusters also had implications for survival and remission duration in both pediatric and adult populations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Laurent Gauthier, Angela Virone-Oddos, Jochen Beninga, Benjamin Rossi, Celine Nicolazzi, Celine Amara, Audrey Blanchard-Alvarez, Nicolas Gourdin, Jacqueline Courta, Alexandra Basset, Magali Agnel, Franceline Guillot, Gwendoline Grondin, Helene Bonnevaux, Anne-Laure Bauchet, Ariane Morel, Yannis Morel, Marielle Chiron, Eric Vivier
Summary: Researchers have developed a novel natural killer cell engager (NKCE) that targets leukemia cells and has potent antitumor activity without toxicity, suggesting its potential for clinical development.
NATURE BIOTECHNOLOGY
(2023)
Article
Oncology
Daniel Cacic, Hakon Reikvam, Oddmund Nordgard, Peter Meyer, Tor Hervig
Summary: The study demonstrates that platelet microparticles can alter the behavior and activity of THP-1 cells, contributing to the development of acute myelogenous leukemia and resistance to chemotherapy. This finding highlights the potential role of platelet microparticles as a target for treatment in leukemia cases.
Article
Biochemistry & Molecular Biology
Maria Ines Costa, Beatriz Santos Lapa, Joana Jorge, Raquel Alves, Isabel Marques Carreira, Ana Bela Sarmento-Ribeiro, Ana Cristina Goncalves
Summary: Zinc plays a dual role in modulating the DNA damage response in acute myeloid leukemia (AML), increasing genotoxicity and cytotoxicity in leukemia cells while preventing damage accumulation in normal cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Zi-Jie Long, Jun-Dan Wang, Sheng-Xiang Qiu, Yi Zhang, Si-Jin Wu, Xin-Xing Lei, Ze-Wei Huang, Jia-Jie Chen, Yong-Liang Yang, Xiang-Zhong Zhang, Quentin Liu
Summary: This study found that dietary gamma-mangostin can induce immunogenic cell death (ICD) and activate cGAS signaling through DNA damage response and epigenetic modification. Additionally, gamma-mangostin promotes transcription of chemokines, activates and recruits CD8(+) T cells, thereby provoking anti-tumor immunity and potentially preventing and treating leukemia.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Medical Laboratory Technology
Jiang Yu, Wen-XU Chen, Wen-Jing Xie, Rong-Wei Chen, Dan-Qi Lin, Wei-Wei You, Wei-Lin Ye, Hong-Qin Zhang, Dong-Hong Lin, Jian-Ping Xu
Summary: Silencing of CrkL effectively increases apoptosis induced by doxorubicin and reverses doxorubicin resistance in K562/ADR cells. Knockdown CrkL suppresses the PI3K/Akt/MRP1 signaling pathway, indicating a potential novel strategy for intervention chemoresistance in myelogenous leukemia during chemotherapy. Overexpression of MRP1 reduces apoptosis rate and reverses inhibitory effects of doxorubicin resistance caused by CrkL siRNA on K562/ADR cells.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2021)
Article
Biochemistry & Molecular Biology
Beatriz Santos Lapa, Maria Ines Costa, Diana Figueiredo, Joana Jorge, Raquel Alves, Ana Raquel Monteiro, Beatriz Serambeque, Mafalda Laranjo, Maria Filomena Botelho, Isabel Marques Carreira, Ana Bela Sarmento-Ribeiro, Ana Cristina Goncalves
Summary: The non-homologous end joining pathway, with DNA-PK playing a critical role, is important for repairing DNA double-strand breaks (DSB). This study indicates that AZD-7648 holds promise as a potential therapy for myeloid leukemias, although there are variations in drug sensitivity among different cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Zach H. Gray, Damayanti Chakraborty, Reuben R. Duttweiler, Gulnaz D. Alekbaeva, Sedona E. Murphy, Kashish Chetal, Fei Ji, Benjamin I. Ferman, Madison A. Honer, Zhentian Wang, Cynthia Myers, Renhong Sun, H. Umit Kaniskan, Monika Maria Toma, Elena A. Bondarenko, John N. Santoro, Christopher Miranda, Megan E. Dillingham, Ran Tang, Or Gozani, Jian Jin, Tomasz Skorski, Cihangir Duy, Hayan Lee, Ruslan I. Sadreyev, Johnathan R. Whetstine
Summary: MLL/KMT2A amplifications and rearrangements in leukemia are regulated by the balance of histone H3 lysine 9 mono- and di-methylation (H3K9me1/2) at the MLL/KMT2A locus. This balance is controlled by the interaction between lysine demethylase KDM3B and methyltransferase G9a/EHMT2. This study provides insights into the molecular mechanisms of MLL/KMT2A alterations and identifies potential drug targets for therapeutic intervention.
Review
Oncology
Hagop M. Kantarjian, Tapan M. Kadia, Courtney D. DiNardo, Mary Alma Welch, Farhad Ravandi
Summary: Research on acute myeloid leukemia (AML) has progressed rapidly, with the US FDA approving 10 drugs for various AML indications since 2017. Different subsets of AML require tailored treatment strategies, including young patients fit for chemotherapy and older patients not suitable for intensive treatment, with combination therapy showing promising results.
Article
Multidisciplinary Sciences
Nichole Owen, Irina G. Minko, Samantha A. Moellmer, Sydney K. Cammann, R. Stephen Lloyd, Amanda K. McCullough
Summary: Human clinical trials suggest that inhibition of enzymes in the DNA base excision repair (BER) pathway, such as PARP1 and APE1, can be useful in anticancer strategies when combined with certain DNA-damaging agents. Specifically, in acute myeloid leukemia (AML), AML cell lines deficient in OGG1 have enhanced sensitivity to cytarabine (Ara-C) treatment. This enhanced cytotoxicity is likely due to the insertion of Ara-C opposite unrepaired 8-oxo-dG in OGG1-deficient AML cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Environmental Sciences
Yan Jin, Yiting Li, Shiyi He, Yijun Ge, Yun Zhao, Ke Zhu, Andong He, Siyu Li, Siyu Yan, Chao Cao
Summary: PM2.5 induces airway inflammation and DNA damage, and the ATM gene plays a role in promoting this inflammation.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Cell Biology
Lin Feng, Ruxin Ding, Xuan Qu, Yuanchun Li, Tong Shen, Lei Wang, Ruikai Li, Juan Zhang, Yi Ru, Xin Bu, Yang Wang, Min Li, Wenqi Song, Liangliang Shen, Pengxia Zhang
Summary: TXNIP is a novel target gene in CML treatment that, when restored, enhances sensitivity to imatinib and impairs the survival of resistant cells by blocking glycolysis and glucose oxidation.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Sifaddin M. R. Konis, Jonathan R. Hughes, Jason L. Parsons
Summary: TRIM26 plays a central role in determining the response to different forms of oxidative stress by regulating DNA glycosylase levels required for an efficient base excision repair (BER) response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Mirjam E. van de Velde, Sofia el Manouni el Hassani, Gert Jan L. Kaspers, Jorrit Broertjes, Marc A. Benninga, Nanne K. H. de Boer, Andries E. Budding, Tim G. J. de Meij
Summary: The potential of intestinal microbiota and fecal volatile organic compounds (VOCs) analyses in predicting bloodstream infections (BSIs) in pediatric leukemia patients was explored. Reduced microbial diversity and stability of Bacteroidetes were observed in patients who developed BSI. Pantoea was identified as a potential marker for BSI. Significant differences in fecal VOC profiles were measured between BSI cases and non-BSI controls.
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
(2022)
Article
Oncology
Kim Klein, H. Berna Beverloo, Martin Zimmermann, Susana C. Raimondi, Christine von Neuhoff, Valerie Haas, Romy van Weelderen, Jacqueline Cloos, Jonas Abrahamsson, Yves Bertrand, Michael Dworzak, Alcira Fynn, Brenda Gibson, Shau-Yin Ha, Christine J. Harrison, Henrik Hasle, Sarah Elitzur, Guy Leverger, Alexei Maschan, Bassem Razzouk, Dirk Reinhardt, Carmelo Rizzari, Pter Smisek, Ursula Creutzig, Gertjan J. L. Kaspers
Summary: Cytogenetic profiles and karyotypic changes at relapse play a significant role in predicting survival outcomes for children with relapsed AML, with certain abnormalities associated with better or worse prognosis. Early treatment response, time to relapse, and cytogenetic profile at relapse are important prognostic factors, outweighing karyotypic instability per se.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Hematology
Tara White, Gertjan Kaspers, Jonas Abrahamsson, Nira Arad-Cohen, Daniela Cianci, Jose Fernandez, Shau-Yin Ha, Henrik Hasle, Barbara De Moerloose, C. Michel Zwaan, Bianca F. Goemans
Summary: This study analyzed data from 157 pediatric AML patients and found that the 1-year and 5-year overall survival rates were 22% and 14%, respectively. Factors influencing prognosis for patients receiving third-line therapy included late relapse, type of third-line treatment, FLT3 mutational status, and original treatment protocol. These findings provide a baseline for evaluating the effectiveness of emerging therapies for treating refractory first relapsed and second relapsed pediatric AML.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Editorial Material
Oncology
Gertjan J. L. Kaspers
EXPERT REVIEW OF ANTICANCER THERAPY
(2022)
Article
Oncology
Maya Schulpen, Bianca F. Goemans, Gertjan J. L. Kaspers, Marc H. G. P. Raaijmakers, C. Michel Zwaan, Henrike E. Karim-Kos
Summary: The study found that AYAs diagnosed with AML in the Netherlands had significantly lower survival rates compared to children, with a 60% higher risk of excess mortality for AYAs. Despite improvements in care over time, there still exists a substantial survival gap between the two age groups. However, early mortality rates did not differ between children and AYAs.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Aniek Uittenboogaard, Festus Njuguna, Saskia Mostert, Sandra Langat, Mirjam E. van de Velde, Gilbert Olbara, Terry A. Vik, Gertjan J. L. Kaspers
Summary: The study assessed the treatment outcomes of children with WT at a large hospital in Kenya and found that despite late-stage diagnosis, the prognosis of children with WT has improved over the years. The treatment protocol included chemotherapy and surgery, with patients receiving radiation therapy showing higher survival rates.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Oncology
Katerina Bakunina, Hein Putter, Jurjen Versluis, Eva A. S. Koster, Bronno van der Holt, Markus G. Manz, Dimitri A. Breems, Bjorn T. Gjertsen, Jacqueline Cloos, Peter J. M. Valk, Jakob Passweg, Thomas Pabst, Gert J. Ossenkoppele, Bob Lowenberg, Jan J. Cornelissen, Liesbeth C. de Wreede
Summary: The study found that using clofarabine treatment in patients with acute myeloid leukemia can reduce the risk of relapse, regardless of individual MRD status or subsequent treatment method. However, during the period from CR to receiving alloSCT, non-relapse mortality was higher in patients receiving clofarabine treatment. Overall, clofarabine treatment has been shown to be beneficial in terms of current leukemia-free survival.
Review
Oncology
Aniek Uittenboogaard, Celine L. G. Neutel, Johannes C. F. Ket, Festus Njuguna, Alwin D. R. Huitema, Gertjan J. L. Kaspers, Mirjam E. van de Velde
Summary: This systematic review and meta-analysis investigates the influence of pharmacogenomic parameters on the development of VIPN in children with cancer. The study found that SNPs in genes related to transporter, metabolism, cytoskeleton, hereditary neuropathy, and even unrelated genes were associated with VIPN. However, there were limitations in comparing and interpreting the results due to heterogeneity in the study population, treatment protocol, and assessment methods. Independent replication is needed to validate the clinical significance of the reported associations.
Article
Medical Laboratory Technology
Costa Bachas, Carolien Duetz, Margot F. van Spronsen, Jan Verhoeff, Juan J. Garcia Vallejo, Joop H. Jansen, Jacqueline Cloos, Theresia M. Westers, Arjan A. van de Loosdrecht
Summary: Through mass cytometry and computational data analysis, we were able to characterize HSPC subsets in MDS and identify leukemia stem cell populations based on their immunophenotype. Stem cells in MDS that display leukemia-associated features may predict the risk of developing AML.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Oncology
Elien Heylen, Paulien Verstraete, Linde Van Aerschot, Shauni L. Geeraerts, Tom Venken, Kalina Timcheva, David Nittner, Jelle Verbeeck, Jonathan Royaert, Marion Gijbels, Anne Uyttebroeck, Heidi Segers, Diether Lambrechts, Jan Cools, Kim De Keersmaecker, Kim R. Kampen
Summary: This study identifies the transcription factor NKX2-1 as a driver of serine/glycine synthesis addiction in cancer cells. NKX2-1 binds and transcriptionally upregulates serine/glycine synthesis enzyme genes, enabling cells expressing NKX2-1 to proliferate and invade in serine/glycine-depleted conditions. The findings reveal the unique metabolic rewiring of NKX2-1-driven cancers and provide possibilities for new therapeutic strategies.
BRITISH JOURNAL OF CANCER
(2023)
Review
Obstetrics & Gynecology
Katja C. E. Drechsel, Maxime C. F. Pilon, Francis Stoutjesdijk, Salena Meivis, Linda J. Schoonmade, William Hamish B. Wallace, Eline van Dulmen-den Broeder, Auke Beishuizen, Gertjan J. L. Kaspers, Simone L. Broer, Margreet A. Veening
Summary: This narrative review summarized existing literature on reproductive function in young Hodgkin lymphoma survivors. The results showed that female survivors had a high incidence of premature ovarian insufficiency, while male survivors often experienced post-treatment azoospermia. Higher doses of chemotherapeutic agents and pelvic radiotherapy were associated with impaired reproductive ability.
HUMAN REPRODUCTION UPDATE
(2023)
Article
Biochemistry & Molecular Biology
Judith Hounjet, Arjan J. Groot, Jolanda P. Piepers, Onno Kranenburg, Danny A. Zwijnenburg, Francesca A. Rapino, Jan B. Koster, Kim R. Kampen, Marc A. Vooijs
Summary: The activation of the Notch receptor requires both the ?-secretase cleavage and vesicular trafficking. A novel regulator of Notch signaling, Dmt1, is found to be essential for Notch activation and is involved in endolysosomal trafficking. The isoforms of Dmt1 act as binary switches to control Notch cell fate decisions.
Review
Biochemistry & Molecular Biology
Paulien Verstraete, Kim De Keersmaecker, Kim Rosalie Kampen
Summary: Cancer cells increase their production of serine and glycine through metabolic rewiring, specifically through upregulation of de novo serine/glycine synthesis. This review focuses on the upregulation of endogenous serine/glycine production in acute leukemia, including T-cell acute leukemia (T-ALL) and acute myeloid leukemia (AML). Genetic lesions directly impacting serine/glycine addiction in acute leukemia have been identified, along with indirect regulation of de novo serine/glycine synthesis.
Article
Hematology
Jesse M. Tettero, Sylvie Freeman, Veit Buecklein, Adriano Venditti, Luca Maurillo, Wolfgang Kern, Roland B. Walter, Brent L. Wood, Christophe Roumier, Jan Philippe, Barbara Denys, Jeffrey L. Jorgensen, Marie C. Bene, Francis Lacombe, Adriana Plesa, Monica L. Guzman, Agnieszka Wierzbowska, Anna Czyz, Lok Lam Ngai, Adrian Schwarzer, Costa Bachas, Jacqueline Cloos, Marion Subklewe, Michaela Fuering-Buske, Francesco Buccisano
Summary: Experts from the MRD Working Party of the European LeukemiaNet evaluated the key factors for accurate MFC-MRD measurement in acute myeloid leukemia (AML) and provided recommendations to ensure quality and reproducibility of results. The recommendations were tested by comparing two 8-color MRD panels in multiple laboratories, confirming their feasibility.
