Article
Hematology
Orsola di Martino, Haixia Niu, Gayla Hadwiger, Heikki Kuusanmaki, Margaret A. Ferris, Anh Vu, Jeremy Beales, Carl Wagner, Maria P. Menendez-Gutierrez, Mercedes Ricote, Caroline Heckman, John S. Welch
Summary: Natural RXRA ligands were found in murine MLL-AF9-derived myelomonocytic leukemias in vivo, acting as tumor suppressors when coexisting with receptors. Pharmacologic retinoid responses could be optimized by targeting both RXR ligands and RARA ligands, inducing leukemic maturation or apoptosis. Combination synergy of RARA and RXRA activation was associated with improved survival in AML, although tolerability of bexarotene administration in mice remained a concern.
Review
Cell Biology
Zeinab Wehbe, Foued Ghanjati, Christian Flotho
Summary: JMML is a malignant myeloproliferative disorder arising in infants and young children, notoriously refractory to conventional cytostatic therapy. Allogeneic hematopoietic stem cell transplantation remains the mainstay of curative therapy. Alternative therapeutic approaches with small epigenetic molecules have recently entered the stage and show surprising efficacy, highlighting the need for preclinical models to test novel agents.
Article
Medical Laboratory Technology
Orianne Wagner-Ballon, Peter Bettelheim, Jeroen Lauf, Frauke Bellos, Matteo Della Porta, Erica Travaglino, Dolores Subira, Irene Nuevo Lopez, Sihem Tarfi, Theresia M. Westers, Ulrika Johansson, Katherina Psarra, Serafeim Karathanos, Sergio Matarraz, Enrique Colado, Monali Gupta, Robin Ireland, Wolfgang Kern, Arjan A. Van de Loosdrecht
Summary: This multicenter study demonstrates the robustness of the monocyte assay in distinguishing chronic myelomonocytic leukemia from other causes of monocytosis. It also confirms the possibility of using this assay in bone marrow samples.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Immunology
Wanjing Cen, Felix Umrath, Antonio Jose Salgado, Siegmar Reinert, Dorothea Alexander
Summary: The secretomes derived from osteogenically induced jaw periosteum-derived mesenchymal stem cells (JPCs) have inhibitory effects on the maturation of monocyte-derived dendritic cells (MoDCs), as they reduce the formation of MoDC clusters and down-regulate the expression of CD80, CD86, and CD197 on MoDCs. The secretomes also enhance the uptake capacity of MoDCs and promote the expansion of regulatory T cells. Furthermore, the secretomes affect the gene expression of MoDCs, up-regulating CD209, HLA-DRA, CSF3, IL10, and IL8, and down-regulating IFN gamma and IL12B.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Medicine, General & Internal
Sao-Chih Ni, Chi-Yuan Yao, Feng-Ming Tien, Chien-Chin Lin
Summary: We report a case of a 70-year-old man with acute myelomonocytic leukemia, whose leukemic blasts at initial presentation had atypical morphology, resembling lymphoblasts, with scant cytoplasm and inconspicuous cytoplasmic granules. Our report highlights the importance of recognizing the possibility of atypical blast morphology in acute myelomonocytic leukemia.
CLINICAL CASE REPORTS
(2023)
Article
Cell Biology
Hai P. Nguyen, Frances Lin, Danielle Yi, Ying Xie, Jennie Dinh, Pengya Xue, Hei Sook Sul
Summary: Adipose tissue mass and adiposity change throughout lifespan, with visceral adipose tissue (VAT) increasing and subcutaneous adipose tissue (SAT) decreasing with aging. A regulatory cell population called ARCs emerges in aging SAT, expressing progenitor markers but lacking adipogenic capacity, inhibiting proliferation and differentiation of neighboring adipose precursors. Pu.1 is identified as a driving factor for ARC development, correlating with aging-associated loss of SAT.
DEVELOPMENTAL CELL
(2021)
Article
Medicine, General & Internal
Alessandra Romano, Michele Giusti, MaryAnn Di Giorgio, Giovanni Lumera, Nunziatina Laura Parrinello, Sebastiano Cosentino, Massimo Ippolito, Loredana Villari, Giuseppe Alberto Palumbo, Francesco Di Raimondo, Salvatore Santo Signorelli
Summary: In CMML, neoplastic monocytes can be distinguished based on their immunophenotype. Supportive care myeloid growth factors in concomitant extranodal non-Hodgkin Lymphoma are safe.
CLINICAL CASE REPORTS
(2021)
Article
Immunology
Bristy Sabikunnahar, Sydney Caldwell, Stella Varnum, Tyler Hogan, Alexei Cooper, Karolyn G. Lahue, Joseph J. Bivona, Phoebe M. Cousens, Menelaos Symeonides, Bryan A. Ballif, Matthew E. Poynter, Dimitry N. Krementsov
Summary: This study characterized a mouse long noncoding RNA named U90926. The expression of U90926 was induced in macrophages and dendritic cells by TLR activation. U90926 deficiency resulted in increased sickness responses and mortality in an endotoxic shock model, potentially mediated by the secreted U9-ORF protein.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Oncology
Marie Sabatier, Emeline Boet, Sonia Zaghdoudi, Nathan Guiraud, Alexis Hucteau, Nathaniel Polley, Guillaume Cognet, Estelle Saland, Laura Lauture, Thomas Farge, Ambrine Sahal, Vera Pancaldi, Emeline Chu-Van, Florence Castelli, Sarah Bertoli, Pierre Bories, Christian Recher, Helena Boutzen, Veronique Mansat-De Mas, Lucille Stuani, Jean-Emmanuel Sarry
Summary: Around 15% of AML patients have mutations in IDH genes, leading to the production of the oncometabolite 2-HG. While inhibitors of mutant IDH enzymes have been approved, many patients do not respond due to mechanisms of resistance such as 2-HG rebound. This study shows that 2-HG activates VDR in IDH mutant AML cells, increasing sensitivity to vitamin D and ATRA combination therapy, offering a new approach for treating AML patients in this subgroup.
Article
Immunology
Omid Teymournejad, Zhaotao Li, Pavani Beesetty, Ching Yang, Christopher P. P. Montgomery
Summary: Staphylococcus aureus infections pose a significant public health concern, necessitating the development of an urgently needed vaccine. However, previous vaccines have failed to protect humans against S. aureus despite promising results in preclinical models. This study reveals that prior exposure to S. aureus negatively impacts vaccine-mediated protection, with specific inhibition observed in the vaccine targeting alpha-hemolysin (Hla) and its expression during primary infection. Surprisingly, this inhibition occurs at the level of vaccine-elicited effector T cells, which can be rescued by the T cell-stimulating adjuvant CAF01. These findings shed light on the potential mechanism behind the translation failure of S. aureus vaccines from mouse models to clinical practice and propose a path forward to prevent these devastating infections.
Article
Oncology
Gatha Thacker, Mukul Mishra, Akshay Sharma, Anil Kumar Singh, Sabyasachi Sanyal, Arun Kumar Trivedi
Summary: The study demonstrates that CDK2 potentiates SKP2-mediated C/EBP alpha degradation in AML, leading to differentiation block. CDK2 promotes C/EBP alpha ubiquitination and reduces its protein levels, while simultaneous SKP2 depletion restores C/EBP alpha expression and function.
Article
Cell Biology
Dylan Kwart, Jing He, Subhashini Srivatsan, Clarissa Lett, Jacquelynn Golubov, Erin M. Oswald, Patrick Poon, Xuan Ye, Janelle Waite, Arielle Glatman Zaretsky, Sokol Haxhinasto, Elsa Au-Yeung, Namita T. Gupta, Joyce Chiu, Christina Adler, Samvitha Cherravuru, Evangelia Malahias, Nicole Negron, Kathryn Lanza, Angel Coppola, Min Ni, Hang Song, Yi Wei, Gurinder S. Atwal, Lynn Macdonald, Nicole Stokes Oristian, William Poueymirou, Vladimir Jankovic, Matthew Fury, Israel Lowy, Andrew J. Murphy, Matthew A. Sleeman, Bei Wang, Dimitris Skokos
Summary: This study identifies endogenous cancer cell-derived type I interferons (IFNs) as regulators of monocyte functional polarization, which in turn influences the efficacy of immunotherapies. By analyzing single-cell transcriptomic data from human and mouse tumors, the researchers distinguish and separate immunostimulatory from immunosuppressive tumor monocytes based on surface marker expression. They show that cancer cell-derived IFNs regulated by cGAS-STING pathway can polarize immunostimulatory monocytes and demonstrate that immunosuppressive monocytes can convert into immunostimulatory monocytes upon cancer cell-intrinsic cGAS-STING activation. Moreover, the study finds that human cancer cells can produce type I IFNs that polarize monocytes, and the immunostimulatory monocyte gene signature is enriched in patient tumors that respond to anti-PD-1 immunotherapy.
Article
Veterinary Sciences
Masaki Maezawa, Ai Nakamichi, Nao Akiyama, Michihito Tagawa, Ken-ichi Watanabe, Yoshiyasu Kobayashi, Hisashi Inokuma
Summary: A 4-year, 7-month-old Holstein cow was diagnosed with acute myelomonocytic leukemia (AMML) despite ANAE-negative tumor cells. Through cytological, hematological, and pathological examination, abnormal cell proliferation associated with this disease was identified.
JOURNAL OF VETERINARY MEDICAL SCIENCE
(2021)
Article
Cell Biology
Shouyun Li, Xue Yang, Shuang Liu, Yirui Chen, Haiyan Xing, Kejing Tang, Zheng Tian, Yingxi Xu, Qing Rao, Min Wang, Jianxiang Wang
Summary: The study found that expression of TR in mouse hematopoietic progenitors induces blockade of differentiation with enhanced proliferative capacity in vitro and established a new mouse leukemia model that more accurately recapitulates human APL. Despite sensitivity to ATRA-induced cell differentiation, neither ATRA monotherapy nor combination with As2O3 confers survival benefit to TR mice, consistent with poor clinical outcomes of APL patients with the TR fusion gene. Based on histone deacetylation phenotypes implied by bioinformatic analysis, HDAC inhibitors demonstrated significant survival superiority in the survival of TR mice, providing insights into clinical efficacy against rare types of APL.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Ian Edward Gentle, Isabel Moelter, Mohamed Tarek Badr, Konstanze Dohner, Michael Lubbert, Georg Hacker
Summary: Mutations in the transcription factor C/EBP alpha have been shown to substantially alter differentiation of progenitors into mature neutrophils and enhance transcriptional activity, particularly the K313 mutation. These results indicate that the C/EBP alpha-K313 mutation can regulate target gene expression through a network of other transcription factors, contributing to the development of AML.
CELL DEATH & DISEASE
(2021)
Article
Hematology
Lorric Delage, Mireille Lambert, Cindy Kundlacz, Dimitri Chartoire, Axel Conchon, Lucas Gorka, Patrick Auberger, Arnaud Jacquel, Carole Soussain, Olivier Destaing, Henri -Jacques Delecluse, Susanne Delecluse, Samir Merabet, Alexandra Traverse-Glehen, Gilles Salles, Emmanuel Bachy, Marc Billaud, Herve Ghesqueres, Jean-Pierre Rouaut, Pierre Sujobert
Summary: Understanding the role of mutated genes is crucial for improving cancer treatment. This study focuses on the BTG1 gene, which is frequently mutated in DLBCL. The researchers found that BTG1 deletion accelerates the development of lymphoproliferative disease driven by Bcl2 overexpression. They also discovered that BCAR1 is a partner of BTG1 and that overactivation of the BCAR1-RAC1 pathway increases cell migration ability. The SRC inhibitor dasatinib can target these modifications, providing new therapeutic opportunities for BTG1 mutated DLBCL.
Letter
Hematology
Laure Goursaud, Celine Berthon, Bruno Quesnel
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Oncology
Marc Colonna, Pascale Grosclaude, Anne-Marie Bouvier, Juste Aristide Goungounga, Valerie Jooste
Article
Oncology
Raphael Itzykson, Valeria Santini, Sylvain Thepot, Lionel Ades, Cendrine Chaffaut, Aristoteles Giagounidis, Margot Morabito, Nathalie Droin, Michael Luebbert, Rosa Sapena, Stanislas Nimubona, Jean Goasguen, Eric Wattel, Gina Zini, Jose Miguel Torregrosa Diaz, Ulrich Germing, Anna Maria Pelizzari, Sophie Park, Nadja Jaekel, Georgia Metzgeroth, Francesco Onida, Robert Navarro, Andrea Patriarca, Aspasia Stamatoullas, Katharina Goetze, Martin Puttrich, Sandra Mossuto, Eric Solary, Silke Gloaguen, Sylvie Chevret, Fatiha Chermat, Uwe Platzbecker, Pierre Fenaux
Summary: This study compared two treatment methods for chronic myelomonocytic leukemia and found that using DAC significantly reduced the risk of CMML transforming into acute myelomonocytic leukemia.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Zakia Aid, Elie Robert, Cecile K. Lopez, Maxence Bourgoin, Fabien Boudia, Melchior Le Mene, Julie Riviere, Marie Baille, Salima Benbarche, Laurent Renou, Alexandre Fagnan, Cecile Thirant, Laetitia Federici, Laure Touchard, Yann Lecluse, Anton Jetten, Birgit Geoerger, Helene Lapillonne, Eric Solary, Muriel Gaudry, Soheil Meshinchi, Francoise Pflumio, Patrick Auberger, Camille Lobry, Arnaud Petit, Arnaud Jacquel, Thomas Mercher
Summary: Pediatric acute myeloid leukemia expressing the ETO2::GLIS2 fusion oncogene has a poor prognosis. The expression of ETO2::GLIS2 leads to activation of CASP3 and increased cell death. Inhibiting both BCL2 and MCL1 is necessary to prevent disease progression in vivo, suggesting a potential therapeutic strategy for this aggressive pediatric AML subgroup.
Article
Oncology
Benjamin Tournier, Romain Aucagne, Caroline Truntzer, Cyril Fournier, Francois Ghiringhelli, Caroline Chapusot, Laurent Martin, Anne Marie Bouvier, Sylvain Manfredi, Valerie Jooste, Mary B. Callanan, Come Lepage
Summary: Using DNA methylation-based screening, researchers have developed a classifier that can segregate stage II colon cancer into four sub-classes. They identified hypermethylation at specific CpG sites in CDH17 and LRP2 genes that independently confer increased or reduced risk of cancer recurrence. Functional enrichment and immune cell infiltration analyses revealed distinct molecular features in each sub-class.
Article
Hematology
Giovanni A. Botten, Yuannyu Zhang, Kseniia Dudnyk, Yoon Jung Kim, Xin Liu, Jacob T. Sanders, Aygun Imanci, Nathalie Droin, Hui Cao, Pranita Kaphle, Kathryn E. Dickerson, Kirthi R. Kumar, Mingyi Chen, Weina Chen, Eric Solary, Peter Ly, Jian Zhou, Jian Xu
Summary: Structural variants (SVs) can rewire chromatin topologies through enhancer hijacking, leading to the activation of oncogenes in human cancers, including hematologic malignancies; however, the molecular determinants for the functional output of enhancer hijacking remain poorly understood due to the lack of tools to assess their effects on gene regulation and chromatin organization.
Article
Oncology
Alexandre Thobie, Anne-Marie Bouvier, Veronique Bouvier, Valerie Jooste, Lucille Queneherve, Jean-Baptiste Nousbaum, Arnaud Alves, Olivier Dejardin
Summary: The surgical volume of hospitals has a significant impact on the survival rate of patients with pancreatic ductal adenocarcinoma (PDAC). High-volume hospitals have better survival rates, while low-volume hospitals have higher post-operative mortality. The centralization of pancreatic surgery is a complex issue.
Article
Biochemistry & Molecular Biology
Stephanie Solier, Michele Mondini, Lydia Meziani, Arnaud Jacquel, Catherine Lacout, Tom Vanden Berghe, Yvon Jule, Jean-Claude Martinou, Gerard Pierron, Julie Riviere, Marc Deloger, Corinne Dupuy, Anny Slama-Schwok, Nathalie Droin, Peter Vandenabeele, Patrick Auberger, Eric Deutsch, Jamel El-Benna, Pham My-Chan Dang, Eric Solary
Summary: Circulating monocytes are recruited to damaged tissues to generate macrophages that modulate disease progression. Activation of caspase-3 and caspase-7, located near mitochondria, is involved in the generation of monocyte-derived macrophages stimulated by Colony-stimulating factor-1 (CSF-1). A non-conventional pathway that involves caspases and activates NOX2 is responsible for CSF1-driven monocyte differentiation, and targeting this pathway may have therapeutic implications for modulating macrophage polarization in damaged tissues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Francois Ghiringhelli, Valerie Jooste, Sylvain Manfredi, Audrey Hennequin, Come Lepage, Anne -Marie Bouvier
Summary: This study investigated the epidemiology, treatment, and prognosis of biliary tract cancers over the past decade. The incidence of biliary tract cancers did not vary significantly, except for a slight increase in intrahepatic cholangiocarcinoma in men and a decrease in ampulla cancer. Age, performance status, and hospital type were associated with the likelihood of surgery. Ampulla cancer had higher survival rates compared to other sites.
Article
Immunology
Maxime Samson, Coraline Genet, Marc Corbera-Bellalta, Helene Greigert, Georgina Espigol-Frigole, Claire Gerard, Claudie Cladiere, Roser Alba-Rovira, Marion Ciudad, Pierre-Henry Gabrielle, Catherine Creuzot-Garcher, Georges Tarris, Laurent Martin, Philippe Saas, Sylvain Audia, Bernard Bonnotte, Maria C. Cid
Summary: This study evaluated the effect of Human Monocyte-derived Suppressor Cells (HuMoSC) on inflammation and vascular remodeling in Giant Cell Arteritis (GCA) treatment. The results showed that HuMoSCs or their supernatant could decrease vascular inflammation and remodeling, which may address the unmet need in GCA treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
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)
Article
Medicine, Research & Experimental
Vincent Jachiet, Laure Ricard, Pierre Hirsch, Florent Malard, Laurent Pascal, Odile Beyne-Rauzy, Pierre Peterlin, Alexandre Thibault Jacques Maria, Norbert Vey, Maud D'Aveni, Marie-Pierre Gourin, Sophie Dimicoli-Salazar, Anne Banos, Stefan Wickenhauser, Louis Terriou, Benoit De Renzis, Eric Durot, Shanti Natarajan-Ame, Anne Vekhoff, Laurent Voillat, Sophie Park, Julien Vinit, Celine Dieval, Azeddine Dellal, Vincent Grobost, Lise Willems, Julien Rossignol, Eric Solary, Olivier Kosmider, Nicolas Dulphy, Lin Pierre Zhao, Lionel Ades, Pierre Fenaux, Olivier Fain, Mohamad Mohty, Beatrice Gaugler, Arsene Mekinian
Summary: Background systemic inflammatory and autoimmune diseases (SIADs) occur in a significant proportion of myelodysplastic syndrome (MDS) patients. The recently identified VEXAS syndrome, associated with somatic mutations in UBA1, is characterized by severe inflammatory conditions and hematological abnormalities, including MDS. However, the mechanisms underlying the association between MDS and SIADs are largely unknown. This study aimed to evaluate myeloid immune cell subsets in MDS patients with and without SIAD and compare them to healthy controls.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
