Article
Cell Biology
Meher Bolisetti Gayatri, Navya Naidu Gajula, Suresh Chava, Aramati B. M. Reddy
Summary: This study demonstrates the role of glutamine in modulating the fate of MSCs through the crosstalk between mTOR complexes and identifies a critical switch in signaling. Furthermore, it highlights the importance of glutamine in modulating molecular cues involved in diabetes-induced bone adipogenesis and other secondary complications.
CELL DEATH DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Gwen R. Buel, Huy Q. Dang, John M. Asara, John Blenis, Anders P. Mutvei
Summary: This study found that prolonged deprivation of arginine and/or leucine leads to reactivation of mTORC1 activity, reaching activation levels similar to those observed in nutrient-rich conditions. Surprisingly, this reactivation is independent of amino acid regeneration, but dependent on PI3K/Akt signaling. These findings expand our understanding of the role of mTORC1 in growth-related diseases and suggest that dietary intervention by removing leucine and/or arginine may be an ineffective therapeutic approach.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Physiology
Angelia Szwed, Eugene Kim, Estela Jacinto
Summary: Cells metabolize nutrients for growth and proliferation, with mTOR playing a key role in integrating growth and metabolism through the protein complexes mTORC1 and mTORC2. Study of mTORC1 and mTORC2 has expanded our understanding of cellular metabolism regulation and functions.
PHYSIOLOGICAL REVIEWS
(2021)
Article
Multidisciplinary Sciences
Chih-Yao Chung, Kritarth Singh, Vassilios N. Kotiadis, Gabriel E. Valdebenito, Jee Hwan Ahn, Emilie Topley, Joycelyn Tan, William D. Andrews, Benoit Bilanges, Robert D. S. Pitceathly, Gyorgy Szabadkai, Mariia Yuneva, Michael R. Duchen
Summary: Heteroplasmic mtDNA mutations, specifically the m.3243 A > G mutation, lead to activated PI3K-Akt-mTORC1 pathway in cells, and inhibiting this pathway reduces mutant mtDNA load. Pharmacological inhibition of PI3K, Akt, or mTORC1 can potentially benefit people with the consequences of the m.3243 A > G mutation by reducing mutant mtDNA load and improving cellular bioenergetic function.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Wojciech Wiese, Julia Barczuk, Olga Racinska, Natalia Siwecka, Wioletta Rozpedek-Kaminska, Artur Slupianek, Radoslaw Sierpinski, Ireneusz Majsterek
Summary: The PI3K/Akt/mTOR pathway is crucial in cancer development and can be a potential therapeutic target for leukemia. Recent research indicates that inhibition of this pathway may lead to improved treatment outcomes for leukemia.
Article
Biochemical Research Methods
Milad Ghomlaghi, Guang Yang, Sungyoung Shin, David E. James, Lan K. Nguyen
Summary: The study reveals the critical role of MLST8 in coordinating the assembly and activity of mTORC1 and mTORC2, involving ubiquitination and feedback loops. The findings also demonstrate a dose-dependent relationship between SIN1 and mTORC1 activity, presenting implications for future therapeutic strategies in breast cancer. Furthermore, the research highlights the complex regulatory mechanisms within the PI3K/MTOR signalling network, shedding light on the interplay between different components and the potential for targeted interventions.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Belen Sanz-Castillo, Begona Hurtado, Diana Vara-Ciruelos, Aicha El Bakkali, Dario Hermida, Beatriz Salvador-Barbero, Diego Martinez-Alonso, Jose Gonzalez-Martinez, Clara Santiveri, Ramon Campos-Olivas, Pilar Ximenez-Embun, Javier Munoz, Monica Alvarez-Fernandez, Marcos Malumbres
Summary: This study reveals that the cell cycle kinase MASTL/Greatwall inhibits the activity of the PI3K-AKT signaling pathway by phosphorylating the PP2A/B55 inhibitor ENSA/ARPP19, thus limiting AKT activity. Furthermore, the study finds that MASTL is directly phosphorylated by mTORC1, which limits the dephosphorylation of IRS1 and GRB10 downstream of mTORC1, further restraining AKT activity. This research highlights the importance of the MASTL-PP2A/B55 kinase-phosphatase module in controlling AKT and maintaining metabolic homeostasis.
Article
Biology
Polina Kosillo, Kamran M. Ahmed, Erin E. Aisenberg, Vasiliki Karalis, Bradley M. Roberts, Stephanie J. Cragg, Helen S. Bateup
Summary: The mTOR pathway is crucial for regulating cell growth and metabolism, and it plays a particularly important role in midbrain dopamine neurons. This study investigated the effects of mTORC1 and mTORC2 complexes on dopamine neuron properties. The inhibition of mTORC1 had significant and broad impacts on dopamine neuron structure and function, while the inhibition of mTORC2 had more subtle effects. Disruption of both mTOR complexes resulted in pronounced deficits in dopamine release.
Review
Oncology
Hu Lei, Jiaqi Wang, Jiacheng Hu, Qian Zhu, Yingli Wu
Summary: Recent studies have identified certain DUBs as promising therapeutic targets in hematological malignancies, with the development of potent inhibitors showing promising inhibitory efficacy. Different DUBs play distinct roles in various types of blood cancers, emphasizing the importance of exploring their biological functions for potential therapeutic targets.
BIOMARKER RESEARCH
(2021)
Review
Chemistry, Multidisciplinary
Wenxing Gu, Ruobing Qu, Fenghua Meng, Jeroen J. L. M. Cornelissen, Zhiyuan Zhong
Summary: Hematological malignancies are difficult to treat with traditional methods due to drug resistance, but new polymeric nanomedicines show promise in overcoming these challenges and improving therapeutic outcomes.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Immunology
Jo Caers, Elodie Duray, Louise Vrancken, Guillaume Marcion, Valentina Bocuzzi, Kim De Veirman, Ahmet Krasniqi, Margaux Lejeune, Nadia Withofs, Nick Devoogdt, Mireille Dumoulin, Amelie Eriksson Karlstrom, Matthias D'Huyvetter
Summary: This review discusses the different strategies introduced for the noninvasive detection and treatment of hematological malignancies by radiotheranostic agents, and explores the future applications of these agents.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xiangyu Lu, Junkai Yao, Changxiang Li, Lingwen Cui, Yizhou Liu, Xiangning Liu, Gang Wang, Jianteng Dong, Qiong Deng, Yueyao Hu, Dongqing Guo, Wei Wang, Chun Li
Summary: In this study, it was found that STDP promotes angiogenesis against CMD by promoting macrophage polarization and increasing the secretion of VEGF-A, thereby improving cardiac function.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jin Hwa Cho, Kidae Kim, Sung Ah Kim, Sungryul Park, Bi-Oh Park, Jong-Hwan Kim, Seon-Young Kim, Min Jee Kwon, Myeong Hoon Han, Sung Bae Lee, Byoung Chul Park, Sung Goo Park, Jeong-Hoon Kim, Sunhong Kim
Summary: OTUD5 has been identified as a novel positive regulator of the mTOR complex signaling pathways, playing a role in stabilizing specific proteins to degrade the inhibitory protein DEPTOR of mTOR, affecting physiological phenotypes such as cell size and autophagy. Our results suggest a positive feedback loop between OTUD5 and the mTOR signaling pathway.
CELL DEATH AND DIFFERENTIATION
(2021)
Review
Pharmacology & Pharmacy
Lara J. Bou J. Malhab, Habiba Alsafar, Saleh Ibrahim, Mohamed Rahmani
Summary: Proteolysis targeting chimeras (PROTACs) are small molecules that target proteins and promote their degradation using the proteasome ubiquitin system, exhibiting high selectivity. They have been successful in targeting undruggable proteins and mutations. Thus, PROTACs have emerged as a promising technology for anticancer therapeutics. Many PROTACs have shown potency in degrading oncogenic drivers and have advanced to clinical testing in various cancers, including hematologic malignancies. This review provides a comprehensive summary of recent advances in using PROTACs as therapeutic strategies in hematological malignancies, with a focus on clinically relevant PROTACs and those targeting oncogenic mutants that drive therapy resistance. Limitations and considerations for optimizing PROTAC design are also discussed.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Elena De Marchi, Anna Pegoraro, Elena Adinolfi
Summary: The P2X7 receptor, known for its role in immune responses, has emerged as a critical factor in promoting cancer. Studies have shown a correlation between P2X7 alterations and lymphoproliferative and myeloproliferative diseases. Recent research suggests that P2X7 and its genetic variants could be new biomarkers in hematological malignancies, and that both P2X7 antagonists and agonists could be potential therapeutic tools.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Hematology
Rudy Birsen, Clement Larrue, Justine Decroocq, Natacha Johnson, Nathan Guiraud, Mathilde Gotanegre, Lilia Cantero-Aguilar, Eric Grignano, Tony Huynh, Michaela Fontenay, Olivier Kosmider, Patrick Mayeux, Nicolas Chapuis, Jean Emmanuel Sarry, Jerome Tamburini, Didier Bouscary
Summary: APR 246 is a promising therapeutic agent for myelodysplastic syndromes and acute myeloid leukemia that targets p53 mutated proteins. It has been found to reactivate the transcriptional activity of p53 mutants and induce p53-independent cell death. The study also demonstrates the association between APR 246 and ferroptosis, a recently described cell death process. The detoxification capacity of AML cells to maintain glutathione biosynthesis may play a key role in determining sensitivity to APR 246.
Article
Medical Laboratory Technology
Vincent H. J. van der Velden, Frank Preijers, Ulrika Johansson, Theresia M. Westers, Alan Dunlop, Anna Porwit, Marie C. Bene, Peter Valent, Jeroen te Marvelde, Orianne Wagner-Ballon, Uta Oelschlaegel, Leonie Saft, Sharham Kordasti, Robin Ireland, Eline Cremers, Canan Alhan, Carolien Duetz, Willemijn Hobo, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenshink-Brodersen, Patricia Font, Michael R. Loken, Sergio Matarraz, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Dolores Subira, Denise A. Wells, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Elisabeth Weiss, Wolfgang Kern, Arjan van de Loosdrecht
Summary: This article reviews the progress of flow cytometry (FCM) in the diagnosis of myelodysplastic syndrome (MDS) in recent years, and provides optimal methods and recommendations for sample processing, antibody panels and fluorochromes, and current hardware technologies. These recommendations will facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients, but further standardization and harmonization are needed.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Medical Laboratory Technology
Arjan A. Loosdrecht, Wolfgang Kern, Anna Porwit, Peter Valent, Sharham Kordasti, Eline Cremers, Canan Alhan, Carolien Duetz, Alan Dunlop, Willemijn Hobo, Frank Preijers, Orianne Wagner-Ballon, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenschink-Brodersen, Patricia Font, Ulrika Johansson, Michael R. Loken, Jeroen G. Marvelde, Sergio Matarraz, Kiyoyuki Ogata, Uta Oelschlaegel, Alberto Orfao, Katherina Psarra, Dolores Subira, Denise A. Wells, Marie C. Bene, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Vincent H. J. van der Velden, Theresia M. Westers, Leonie Saft, Robin Ireland
Summary: This article discusses the rationale for including flow cytometry (FCM) in the diagnostic investigation and evaluation of cytopenias and suspected myelodysplastic syndromes (MDS) by the European LeukemiaNet international MDS Flow Working Group. The WHO 2016 classification acknowledges the contribution of FCM in the diagnosis of MDS and its potential usefulness in prognostication, prediction, therapy evaluation, and patient follow-up.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Letter
Hematology
Amira Marouf, Anne Segolene Cottereau, Salim Kanoun, Paul Deschamps, Michel Meignan, Patricia Franchi, David Sibon, Clara Antoine, Thomas Gastinne, Cecile Borel, Mohammad Hammoud, Guillaume Sicard, Romane Gille, Doriane Cavalieri, Aspasia Stamatoullas, Lauriane Filliatre-Clement, Julien Lazarovici, Adrien Chauchet, Luc-Matthieu Fornecker, Sandy Amorin, Mathieu Rocquet, Nicole Raus, Barbara Burroni, Marie Therese Rubio, Didier Bouscary, Philippe Quittet, Rene Olivier Casasnovas, Pauline Brice, Herve Ghesquieres, Jerome Tamburini, Benedicte Deau
Article
Cell Biology
Adrien Grenier, Laury Poulain, Johanna Mondesir, Arnaud Jacquel, Claudie Bosc, Lucille Stuani, Sarah Mouche, Clement Larrue, Ambrine Sahal, Rudy Birsen, Victoria Ghesquier, Justine Decroocq, Fetta Mazed, Mireille Lambert, Mamy Andrianteranagna, Benoit Viollet, Patrick Auberger, Andrew A. Lane, Pierre Sujobert, Didier Bouscary, Jean-Emmanuel Sarry, Jerome Tamburini
Summary: AMPK activation in AML cells triggers the unfolded protein response, leading to repression of oxidative phosphorylation, TCA cycle, and pyrimidine biosynthesis, as well as enhanced mitochondrial apoptotic signaling. Combination therapy with the AMPK activator GSK621 and the Bcl-2 inhibitor venetoclax shows synergistic effects, suggesting therapeutic potential in AML.
Review
Medicine, General & Internal
Jaja Zhu, Sylvain Clauser, Nicolas Freynet, Valerie Bardet
Summary: New generations of hematology analyzers provide cell population data that can be exploited for faster diagnosis and reduction of time-consuming slide reviews in the hematology laboratory.
Article
Medicine, General & Internal
Camille Lours, Laurane Cottin, Margaux Wiber, Valerie Andrieu, Veronique Baccini, Lucile Baseggio, Chantal Brouzes, Bernard Chatelain, Sylvie Daliphard, Odile Fenneteau, Franck Genevieve, Sandrine Girard, Vincent Leymarie, Karim Maloum, Jean-Baptiste Rieu, Gerard Sebahoun, Isabelle Sudaka, Xavier Troussard, Orianne Wagner-Ballon, Soraya Wuilleme, Valerie Bardet, Jean-Francois Lesesve
Summary: This article presents the standardization efforts of the French-speaking Cellular Hematology Group in cellular hematology practices, with a focus on Penis' stain. A national survey was conducted, leading to the proposal of recommendations for insoluble iron detection and quantification in bone marrow. The criteria presented here received strong professional agreement and align with the suggestions of the World Health Organization's classification of hematological malignancies.
Review
Oncology
Jaja Zhu, Pierre Lemaire, Stephanie Mathis, Emily Ronez, Sylvain Clauser, Katayoun Jondeau, Pierre Fenaux, Lionel Ades, Valerie Bardet
Summary: This study proposes an extended MDS-CBC score to improve the diagnosis of myelodysplastic syndromes (MDS) on routine laboratory Complete Blood Counts (CBCs) and optimize smear reviews by including more cell population data parameters from the myeloid lineages.
Review
Medical Laboratory Technology
Anna Porwit, Marie C. Bene, Carolien Duetz, Sergio Matarraz, Uta Oelschlaegel, Theresia M. Westers, Orianne Wagner-Ballon, Shahram Kordasti, Peter Valent, Frank Preijers, Canan Alhan, Frauke Bellos, Peter Bettelheim, Kate Burbury, Nicolas Chapuis, Eline Cremers, Matteo G. Della Porta, Alan Dunlop, Lisa Eidenschink-Brodersen, Patricia Font, Michaela Fontenay, Willemijn Hobo, Robin Ireland, Ulrika Johansson, Michael R. Loken, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Leonie Saft, Dolores Subira, Jeroen te Marvelde, Denise A. Wells, Vincent H. J. van der Velden, Wolfgang Kern, Arjan A. van de Loosdrecht
Summary: Multiparameter flow cytometry (MFC) is an essential method in bone marrow investigation for patients with cytopenia and suspected myelodysplastic syndrome (MDS), providing valuable information for diagnosis and treatment follow-up. This document summarizes recommendations from the ELN iMDS Flow on analytical issues in MFC, including the analysis of different cell subsets and the use of specific markers for MDS diagnosis. Machine-learning-based analytical tools and large uniform datasets are suggested for future research to improve integrated diagnostics and risk stratification in MDS.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Oncology
Clement Larrue, Sarah Mouche, Shan Lin, Federico Simonetta, Nastassja K. Scheidegger, Laury Poulain, Rudy Birsen, Jean-Emmanuel Sarry, Kimberly Stegmaier, Jerome Tamburini
Summary: Mitochondrial fusion is a critical dependency in acute myeloid leukemia (AML). Inhibition of mitochondrial fusion through genetic depletion or pharmacological inhibition showed significant anti-leukemic activity in patient-derived xenograft (PDX) models, without impacting normal hematopoietic cells. Mechanistically, disruption of mitochondrial fusion led to cell cycle arrest and impaired mitochondrial respiration and reactive oxygen species production. These findings suggest that inhibition of mitochondrial fusion holds promise as a therapeutic approach for AML.
Article
Hematology
J. Dufour, S. Choquet, K. Hoang-Xuan, A. Schmitt, G. Ahle, R. Houot, L. Taillandier, R. Gressin, O. Casasnovas, J. P. Marolleau, J. Tamburini, C. Serrier, E. Perez, J. Paillassa, E. Gyan, A. Chauchet, R. Ursu, A. Kas, C. Soussain, C. Houillier
Summary: This nationwide population-based study found rare extracerebral relapses of primary central nervous system lymphomas (PCNSL). The extracerebral relapses were mainly found in visceral organs (particularly testis and breast) and the peripheral nervous system. The prognosis was worse for mixed relapses. The study suggests the use of PET-CT in diagnosis and paired tumor analysis at diagnosis/relapse to better understand the underlying molecular mechanisms.
ANNALS OF HEMATOLOGY
(2023)
Article
Hematology
A. Marouf, N. Molinari, D. Sibon, A. S. Cottereau, S. Kanoun, C. Antoine, P. E. Debureaux, D. Cavalieri, L. M. Fornecker, R. O. Casasnovas, C. Herbaux, S. Amorim, C. Rossi, D. Bouscary, P. Brice, H. Ghesquieres, J. Tamburini, B. Deau
Summary: Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for high-risk relapsed/refractory Hodgkin lymphoma (R/R HL) patients. Maintenance therapy with Brentuximab Vedotin (BV) after ASCT has been shown to improve survival in BV-naive patients. In this study, BV maintenance was compared to tandem transplant strategies and was found to be associated with better survival outcomes in patients with high-risk R/R HL.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Marie Sabatier, Rudy Birsen, Laura Lauture, Sarah Mouche, Paolo Angelino, Jonas Dehairs, Ismael Boussaid, Mael Heiblig, Emeline Boet, Ambrine Sahal, Estelle Saland, Juliana C. Santos, Marc Armengol, Miranda Fernandez-Serrano, Thomas Farge, Guillaume Cognet, Federico Simonetta, Corentin Pignon, Antoine Graffeuil, Celine Mazzotti, Herve Avet-Loiseau, Oceane Delos, Justine Bertrand-Michel, Amelie Chedru, Vilma Dembitz, Paolo Gallipoli, Natasha S. Anstee, Sun Loo, Andrew H. Wei, Martin Carroll, Armelle Goubard, Remy Castellano, Yves Collette, Francois Vergez, Veronique Mansat-De Mas, Sarah Bertoli, Suzanne Tavitian, Muriel Picard, Christian Recher, Nathalie Bourges-Abella, Fanny Granat, Olivier Kosmider, Pierre Sujobert, Benoit Colsch, Carine Joffre, Lucille Stuani, Johannes V. Swinnen, Herve Guillou, Gael Roue, Nawad Hakim, Anne S. Dejean, Petros Tsantoulis, Clement Larrue, Didier Bouscary, Jerome Tamburini, Jean-Emmanuel Sarry
Summary: Although the role of CCAAT-enhancer binding protein α (C/EBPα) in cancer cell and metabolic homeostasis is largely unknown, this study reveals its coordination with FLT3 in lipid anabolism and its regulation of fatty acid biosynthesis and desaturation. Furthermore, FLT3 or C/EBPα inactivation decreases monounsaturated fatty acid incorporation and renders FLT3-mutant AML cells vulnerable to ferroptosis. This finding suggests a promising therapeutic potential for targeting FLT3-mutant AML cells.
Review
Cell Biology
Mathieu Meunier, David Laurin, Sophie Park
Summary: The bone marrow niche plays an important role in the development of myelodysplastic syndromes. Mesenchymal stromal cells secrete extracellular vesicles and their miRNA, affecting the fate of hematopoietic stem cells and contributing to leukemogenesis. Extracellular vesicles containing miRNA and proteins can be used as diagnostic and prognostic markers for MDS. Targeting these vesicles or modulating their secretion may offer potential therapeutic directions for MDS.
Letter
Hematology
Maya Belhadj, Barbara Burroni, Olivier Kosmider, Lise Willems, Marie Temple, Sarah Bertoli, Corentin Orvain, Pierre-Yves Dumas, Celine Berthon, Ludovic Gabellier, Ambroise Marcais, Emmanuel Raffoux, Cecile Pautas, Alexis Genthon, Justine Decroocq, Rudy Birsen, Jerome Tamburini, Didier Bouscary, Adrien Contejean
BRITISH JOURNAL OF HAEMATOLOGY
(2023)