Article
Multidisciplinary Sciences
Qi Jin, Blanca Gutierrez Diaz, Tim Pieters, Yalu Zhou, Sonali Narang, Igor Fijalkwoski, Cristina Borin, Jolien Van Laere, Monique Payton, Byoung-Kyu Cho, Cuijuan Han, Limin Sun, Valentina Serafin, George Yacu, Wouter Von Loocke, Giuseppe Basso, Giulia Veltri, Ingrid Dreveny, Issam Ben-Sahra, Young Ah Goo, Stephanie L. Safgren, Yi-Chien Tsai, Beat Bornhauser, Praveen Kumar Suraneni, Alexandre Gaspar-Maia, Irawati Kandela, Pieter Van Vlierberghe, John D. Crispino, Aristotelis Tsirigos, Panagiotis Ntziachristos
Summary: This study reveals that in T cell acute lymphoblastic leukemia (T-ALL), ubiquitin-specific protease 11 (USP11) forms a complex with USP7 to deubiquitinate the oncogenic lymphocyte cell-specific protein-tyrosine kinase (LCK) and enhance its activity. Impairment of LCK activity leads to increased glucocorticoid receptor (GR) expression and glucocorticoids sensitivity. Additionally, the deubiquitinase activity plays a role in the transcriptional activation of GR target genes.
Article
Hematology
Saara Laukkanen, Alexandra Veloso, Chuan Yan, Laura Oksa, Eric J. Alpert, Daniel Do, Noora Hyvarinen, Karin McCarthy, Abhinav Adhikari, Qiqi Yang, Sowmya Iyer, Sara P. Garcia, Annukka Pello, Tanja Ruokoranta, Sanni Moisio, Sadiksha Adhikari, Jeffrey A. Yoder, Kayleigh Gallagher, Lauren Whelton, James R. Allen, Alex H. Jin, Siebe Loontiens, Merja Heinaniemi, Michelle Kelliher, Caroline A. Heckman, Olli Lohi, David M. Langenau
Summary: This study identified a drug combination of AKT/mTORC1 inhibitors and dasatinib that effectively kills T-cell acute lymphoblastic leukemia (T-ALL) in zebrafish, including relapse and dexamethasone-resistant cases. Clinical trials have shown promising results, indicating that this combination could be an effective therapy for T-ALL in humans.
Review
Cell Biology
Malihe Bagheri, Parisa Zia Sarabi, Mahdieh Mondanizadeh
Summary: MicroRNAs can act as oncogenes or tumor suppressors and may play important roles in acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). This review summarizes potential miRNAs, particularly circulating ones, that are involved in essential signaling pathways in ALL and CLL patients, serving as valuable biomarkers and targets for treatment.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Oncology
Francesco Tamiro, Andrew P. Weng, Vincenzo Giambra
Summary: Leukemia-initiating cells (LIC) are unique cells in different types of leukemia that have self-renewing capabilities and produce tumors, which are functionally distinct from bulk leukemia cells. Current conventional treatments are not effective in eliminating LICs, hence innovative therapeutics targeting LICs hold promise for developing an effective cure for ALL.
Article
Immunology
Alejandra Duarte, Daniela R. Montagna, Mercedes Pastorini, Mercedes Aleman
Summary: This study demonstrates that the SAg enterotoxin E (SEE) can induce apoptosis in neoplastic T cells, specifically in Jurkat cells expressing the Vβ8 TCR. In addition, treatment with SEE significantly reduces tumor growth, decreases infiltration of neoplastic cells, and increases survival in mice. These findings suggest that this strategy could be a potential therapeutic option for the treatment of relapsed T-ALL.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tommaso Colangelo, Patrizio Panelli, Francesco Mazzarelli, Francesco Tamiro, Valentina Melocchi, Elisabetta De Santis, Roberto Cuttano, Orazio Palumbo, Giovanni Rossi, Fabrizio Bianchi, Vincenzo Giambra
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive T-cell malignancy. Recent studies have shown that T-ALL-secreted small extracellular vesicles (sEV) contain NOTCH1-dependent microRNAs (EV-miRs), which regulate oncogenic pathways and promote the expansion and survival of highly proliferative cell subsets, thereby altering the cell heterogeneity and dynamics of leukemia.
Article
Oncology
Mengping Xi, Shanshan Guo, Caicike Bayin, Lijun Peng, Florent Chuffart, Ekaterina Bourova-Flin, Sophie Rousseaux, Saadi Khochbin, Jian-Qing Mi, Jin Wang
Summary: This study found that the HDAC inhibitor chidamide has an anti-tumor effect on T-ALL cells, particularly by inhibiting the NOTCH1-MYC signaling axis. Clinical trial results support that chidamide treatment reduces minimal residual disease in patients and is well tolerated.
FRONTIERS OF MEDICINE
(2022)
Article
Cell Biology
Omar Perbellini, Chiara Cavallini, Roberto Chignola, Marilisa Galasso, Maria T. Scupoli
Summary: This study reveals a high variability in signaling networks across different T-ALL cell lines and provides insight into the characterization of these differences using phospho-specific flow cytometry.
Article
Multidisciplinary Sciences
Samiah Shahid, Wajeehah Shahid, Jawaria Shaheen, M. Waheed Akhtar, Saima Sadaf
Summary: This study explored the potential of circulating mir-146a as a non-invasive biomarker for acute lymphoblastic leukemia (ALL) diagnosis. The overexpression of miR-146a in plasma samples of ALL patients before chemotherapy, with a significant decrease post-treatment, suggests its utility as a diagnostic and prognostic marker for pediatric and adult patients with ALL in the future. Potential targets predicted from miR-146a levels could also be utilized for ALL therapy.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Ling Bai, Lei Zhou, Wei Han, Jingtao Chen, Xiaoyi Gu, Zheng Hu, Yongguang Yang, Wei Li, Xiaoying Zhang, Chao Niu, Yongchong Chen, Hui Li, Jiuwei Cui
Summary: This study investigated the direct effects of TLR9 agonists on B-ALL cells and found that high expression of TLR9 in B-ALL patients is associated with good prognosis. Additionally, CpG 685 was found to induce apoptosis in B-ALL cells by activating C-MYC and BAX. Combination therapy of CpG 685 and imatinib reversed resistance and showed promising results. Therefore, TLR9 and CpG 685 could be potential targets and drugs for B-ALL therapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Fang-Liang Huang, Sheng-Jie Yu, Chia-Ling Li
Summary: Acute lymphoblastic leukemia is a malignant disease characterized by an excessive number of immature lymphocytes, affecting children more often than adults. Autophagy and apoptosis play crucial roles in regulating cancer development by degrading proteins and organelles and leading to cell death. Activating autophagy and apoptosis pathways are the main strategies for ALL treatments, with potential for combining new drugs and traditional chemotherapy for better therapeutic effects.
Article
Biology
Carina Colturato-Kido, Rayssa M. Lopes, Hyllana C. D. Medeiros, Claudia A. Costa, Laura E. L. Prado-Souza, Leticia S. Ferraz, Tiago Rodrigues
Summary: Acute lymphoblastic leukemia (ALL) is an aggressive malignant disorder affecting children and adults, with drug resistance posing a significant clinical problem. Antipsychotic phenothiazines are being explored as potential antitumor drugs, with a focus on inducing autophagy-associated cell death to improve treatment outcomes.
Article
Medicine, Research & Experimental
Baris Ertugrul, Elif Sinem Iplik, Bedia Cakmakoglu
Summary: The study found that succinic acid has apoptotic effects on T-ALL cell lines without significant cytotoxic effects on healthy cells. The apoptotic activity of succinic acid on CCRF-CEM cell line is caspase-3 dependent, while it is not for MOLT-4 cell line.
ARCHIVES OF MEDICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Jeoffrey Pelletier, Marielle Balzano, Jerome Destin, Camille Montersino, Marjorie C. Delahaye, Tony Marchand, Anne-Laure Bailly, Florence Bardin, Emilie Coppin, Armelle Goubard, Remy Castellano, Marjolein J. W. de Bruijn, Jasper Rip, Yves Collette, Patrice Dubreuil, Karin Tarte, Cyril Broccardo, Rudi W. Hendriks, Claudine Schiff, Norbert Vey, Michel Aurrand-Lions, Stephane J. C. Mancini
Summary: B-cell acute lymphoblastic leukemia (B-ALL) is the malignant counterpart of developing B cells in the bone marrow (BM). Galectin-1 (GAL1) expressed in BM niches provides proliferation signals to normal pre-B cells through interaction with the pre-B cell receptor (pre-BCR). In murine and patient-derived xenograft (PDX) models, GAL1 produced by BM niches influences the development of pre-B ALL through pre-BCR-dependent signals, similar to normal pre-B cells. Targeting pre-BCR signaling in combination with cell-autonomous oncogenic pathways improves the treatment response in pre-B ALL PDX. Therefore, non-cell autonomous signals transmitted by BM niches could be potential targets to enhance B-ALL patient survival.
Article
Oncology
Fang-Liang Huang, Sheng-Jie Yu, En-Chih Liao, Long-Yuan Li, Pei-Wen Shen, Chia-Ling Li
Summary: Niclosamide exhibits anti-leukemia effects in T-ALL by regulating apoptosis and autophagy to suppress tumor growth.
Article
Immunology
Florian Gothe, Catherine F. Hatton, Linh Truong, Zofia Klimova, Veronika Kanderova, Martina Fejtkova, Angela Grainger, Venetia Bigley, Joanna Perthen, Dipayan Mitra, Ales Janda, Eva Fronkova, Dusana Moravcikova, Sophie Hambleton, Christopher J. A. Duncan
Summary: The case study presents a child with complete deficiency of the interferon alpha/beta receptor alpha chain (IFNAR1) who experienced fatal systemic hyperinflammation, possibly triggered by live-attenuated viral vaccination. This hyperinflammatory condition, meeting the criteria for hemophagocytic lymphohistiocytosis, is a new phenotype associated with inborn errors of type I interferon immunity.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Allergy
Veronika Kanderova, Tamara Svobodova, Simon Borna, Martina Fejtkova, Vendula Martinu, Jana Paderova, Michael Svaton, Jarmila Kralova, Eva Fronkova, Adam Klocperk, Stepanka Pruhova, Min Ae Lee-Kirsch, Ludmila Hornofova, Miroslav Koblizek, Petr Novak, Olga Zimmermannova, Zuzana Parackova, Anna Sediva, Tomas Kalina, Ales Janda, Jana Kayserova, Marcela Dvorakova, Milan Macek, Petr Pohunek, Petr Sedlacek, Ashleigh Poh, Matthias Ernst, Tomas Brdicka, Ondrej Hrusak, Jan Lebl
Summary: This article reports a new monogenic autoinflammatory disorder caused by a de novo activating mutation in the HCK gene, characterized by cutaneous vasculitis and chronic pulmonary inflammation. The study shows the aberrant functions of mutant HCK and the therapeutic efficacy of the Janus kinase 1/2 inhibitor Ruxolitinib in treating inflammatory lung disease.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Hematology
Martina Fejtkova, Martina Sukova, Katerina Hlozkova, Karolina Skvarova Kramarzova, Marketa Rackova, David Jakubec, Marina Bakardjieva, Marketa Bloomfield, Adam Klocperk, Zuzana Parackova, Anna Sediva, Jahnavi Aluri, Michaela Novakova, Tomas Kalina, Eva Fronkova, Ondrej Hrusak, Hana Malcova, Petr Sedlacek, Zuzana Liba, Martin Kudr, Jan Stary, Megan A. Cooper, Michael Svaton, Veronika Kanderova
Summary: Our study identified a novel mutation c.1715G>T (p.G572V) in the Toll-like receptor 8 (TLR8) gene, which causes an autoimmune and autoinflammatory disorder in a family with monozygotic male twins. In vitro assays confirmed the pathogenicity of the mutation and revealed increased inflammatory responses.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Hematology
Daniela Kuzilkova, Cristina Bugarin, Katerina Rejlova, Axel R. Schulz, Henrik E. Mei, Maddalena Paganin, Alessandra Biffi, Andrea Biondi, Tomas Kalina, Giuseppe Gaipa
Summary: This study utilized single-cell mass cytometry to investigate signal transduction pathways in T-cell acute lymphoblastic leukemia (T-ALL), and found that different cellular clusters exhibited varying responsiveness to therapeutic drugs, which remained consistent during relapse.
Letter
Immunology
Jan Havlin, Aneta Skotnicova, Eliska Dvorackova, Petr Hubacek, Monika Svorcova, Jan Lastovicka, Anna Sediva, Tomas Kalina, Robert Lischke
Article
Immunology
Daniela Kuzilkova, Joan Punet-Ortiz, Pei M. Aui, Javier Fernandez, Karel Fiser, Pablo Engel, Menno C. van Zelm, Tomas Kalina
Summary: This study developed a flow cytometric procedure for standardized quantitative expression profiling of surface antigens on blood leukocyte subsets across multiple research laboratories. The designed tubes can discriminate 27 leukocyte subsets and detect the expression of PE-conjugated CD markers.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Sebastian Boettcher, Robby Engelmann, Georgiana Grigore, Paula Fernandez, Joana Caetano, Juan Flores-Montero, Vincent H. J. van der Velden, Michaela Novakova, Jan Philippe, Matthias Ritgen, Leire Burgos, Quentin Lecrevisse, Sandra Lange, Tomas Kalina, Javier Verde Velasco, Rafael Fluxa Rodriguez, Jacques J. M. van Dongen, Carlos E. Pedreira, Alberto Orfao
Summary: Reproducible expert-independent flow cytometric criteria for differential diagnoses between mature B-cell neoplasms were developed and validated using algorithm-driven classification. The diagnostic algorithm showed high accuracy and predictive values for various diseases, contributing to increased reproducibility in future diagnostics for mature B-cell neoplasms.
Review
Immunology
Angela Deya-Martinez, Jaques G. Riviere, Persio Roxo-Junior, Jan Ramakers, Marketa Bloomfield, Paloma Guisado Hernandez, Pilar Blanco Lobo, Soraya Regina Abu Jamra, Ana Esteve-Sole, Veronika Kanderova, Ana Garcia-Garcia, Mireia Lopez-Corbeto, Natalia Martinez Pomar, Andrea Martin-Nalda, Laia Alsina, Olaf Neth, Peter Olbrich
Summary: This study retrospectively examined pediatric patients with STAT1 GOF who received JAKinib treatment and found potential benefits of JAKinibs for this population. However, further research is needed to establish indications, dosing, and monitoring of JAKinibs.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Letter
Hematology
M. Svaton, M. Sukova, P. Sedlacek, A. Skotnicova, E. Vodickova, R. van Wijk, M. Divoka, R. Mojzikova, T. Kalina, J. Trka, E. Fronkova, J. Stary
BLOOD CELLS MOLECULES AND DISEASES
(2022)
Article
Immunology
Krisztian Csomos, Boglarka Ujhazi, Peter Blazso, Jose L. Herrera, Christopher M. Tipton, Tomoki Kawai, Sumai Gordon, Maryssa Ellison, Kevin Wu, Matthew Stowell, Lauren Haynes, Rachel Cruz, Bence Zakota, Johnny Nguyen, Michelle Altrich, Christoph B. Geier, Svetlana Sharapova, Joseph F. Dasso, Jennifer W. Leiding, Grace Smith, Waleed Al-Herz, Mayra de Barros Dorna, Olajumoke Fadugba, Eva Fronkova, Veronika Kanderova, Michael Svaton, Sarah E. Henrickson, Joseph D. Hernandez, Taco Kuijpers, Snezhina Mihailova Kandilarova, Elizaveta Naumova, Tomas Milota, Anna Sediva, Despina Moshous, Benedicte Neven, Tara Saco, Ravishankar Sargur, Sinisa Savic, John Sleasman, Gauri Sunkersett, Brant R. Ward, Masanobu Komatsu, Stefania Pittaluga, Attila Kumanovics, Manish J. Butte, Michael P. Cancro, Shiv Pillai, Eric Meffre, Luigi D. Notarangelo, Jolan E. Walter
Summary: Patients with partial recombination-activating gene deficiency (pRD) exhibit late-onset autoimmune clinical phenotypes. This study found that pRD patients have a restricted primary B cell receptor repertoire enriched for autoreactivity and clonal persistence. Reduced RAG activity in pRD impairs peripheral tolerance through the generation of a restricted B cell repertoire and persistent antigenic stimulation. This results in widespread B cell dysregulation and activation.
Article
Oncology
Barbora Kvokackova, Radek Fedr, Daniela Kuzilkova, Jan Stuchly, Adela Vavrova, Jiri Navratil, Pavel Fabian, Robert Ondrussek, Petra Ovesna, Jan Remsik, Jan Bouchal, Tomas Kalina, Karel Soucek
Summary: Researchers have developed a comprehensive mass cytometry panel for the detection of phenotypic markers and signaling molecules in triple-negative breast cancer (TNBC). This single-cell proteomic approach allows for a better understanding of TNBC heterogeneity and the tumor microenvironment, and identifies potential therapeutic targets.
MOLECULAR ONCOLOGY
(2023)
Article
Allergy
Tomas Milota, Jitka Smetanova, Aneta Skotnicova, Michal Rataj, Jan Lastovicka, Hana Zelena, Zuzana Parackova, Martina Fejtkova, Veronika Kanderova, Eva Fronkova, Katerina Rejlova, Anna Sediva, Tomas Kalina
Summary: Patients with CVID showed measurable antibody and T-cell immune responses after receiving the BNT162b2 vaccine, but the antibody titers were low and decreased rapidly, while the T-cell response remained stable. The vaccine demonstrated favorable safety and clinical outcomes in preventing severe COVID-19.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Article
Hematology
Bart R. Lubbers, Isabel Dombrink, Tomas Kalina, Mattias Hofmans, Morten S. Bruun, Simon J. Stanworth, Marie C. Bene, Konstanze Dohner, Monika Bruggemann, Elizabeth Macintyre, Jacques J. M. van Dongen
Article
Oncology
Petra Pokorna, Giannoula Lakka Klement, Alzbeta Vasikova, Veronika Kanderova, Marta Jezova, Kristyna Noskova, Peter Mudry, Michal Kyr, Tomas Merta, Viera Bajciova, Zdenka Krenova, Hana Palova, Dalibor Valik, Lenka Zdrazilova Dubska, Ondrej Slaby, Jaroslav Sterba
JCO PRECISION ONCOLOGY
(2022)