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4. Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment

Author

Caye, Aurélie, Rouault-Pierre, Kevin, Strullu, Marion, Lainey, Elodie, Abarrategi, Ander, Fenneteau, Odile, Arfeuille, Chloé, Osman, Jennifer, Cassinat, Bruno, Pereira, Sabrina, Anjos-Afonso, Fernando, Currie, Erin, Ariza-McNaughton, Linda, Barlogis, Vincent, Dalle, Jean-Hugues, Baruchel, André, Chomienne, Christine, Cavé, Hélène, and Bonnet, Dominique

Published
2020
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5. A step towards identifying the true adult murine Mesenchymal Stem Cell

Author

dos Anjos Afonso, Fernando

Subjects
616.02774
Abstract

Research spanning over a few decades has contributed to the discovery and understanding of a population of cells that are precursors of connective tissue cell-types. These cells currently referred as Mesenchymal Stem Cells (MSCs), have also been shown by some researchers to have the capacity to give rise to neuron- and muscle-like cells in vitro, making them very attractive as cellular source for clinical application in regenerative medicine. Despite the intense focus on therapeutic research on going in the MSC field, the biology of these cells remains elusive, especially at its hierarchical organisation. Although some data suggest that MSCs are composed of different sub-populations of progenitors or cells that are prompted to differentiate preferentially into one or few different cell-types in vitro, there is no defined hierarchy proposed yet, especially at the most primitive level. The initial aim of this project was to characterise the adult murine MSC (muMSCs) compartment since most of the studies performed to date were conducted with human cells. During the process of such, a new cell type was found. Under a conventional isolation/culture system a minor sub-population of muMSCs was identified and then characterised (based on the expression of SSEA-1 antigen Stage Specific Embryonic Antigen-1). The data presented strongly suggest that this new sub-population is not only the founder of the MSC compartment but also they are multipotent both in vitro and in vivo. Moreover, this new cell-type can be directly identified from fresh bone marrow thus confirming its true existence in vivo. Detailed study on SSEA-1 pos-MSCs revealed that these cells present several common features with Embryonic Stem Cells (ES) and therefore suggests that a group of cells with embryonic features might persist throughout adult life. The identification/characterisation of these adult murine SSEA-1pos cells should facilitate the identification of a similar cell-type in the human MSC compartment. Furthermore, this study opens new questions on the developmental origin and importance of adult tissue-specific stem cells in the maintenance of tissue homeostasis.

Published
2005

6. Supplemental Information from Frequency and Dynamics of Leukemia-Initiating Cells during Short-term Ex Vivo Culture Informs Outcomes in Acute Myeloid Leukemia Patients

Author

Griessinger, Emmanuel, primary, Anjos-Afonso, Fernando, primary, Vargaftig, Jacques, primary, Taussig, David C., primary, Lassailly, François, primary, Prebet, Thomas, primary, Imbert, Véronique, primary, Nebout, Marielle, primary, Vey, Norbert, primary, Chabannon, Christian, primary, Filby, Andrew, primary, Bollet-Quivogne, Frederic, primary, Gribben, John G., primary, Peyron, Jean-François, primary, and Bonnet, Dominique, primary

Published
2023
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7. Supplemental Table from Frequency and Dynamics of Leukemia-Initiating Cells during Short-term Ex Vivo Culture Informs Outcomes in Acute Myeloid Leukemia Patients

Author

Griessinger, Emmanuel, primary, Anjos-Afonso, Fernando, primary, Vargaftig, Jacques, primary, Taussig, David C., primary, Lassailly, François, primary, Prebet, Thomas, primary, Imbert, Véronique, primary, Nebout, Marielle, primary, Vey, Norbert, primary, Chabannon, Christian, primary, Filby, Andrew, primary, Bollet-Quivogne, Frederic, primary, Gribben, John G., primary, Peyron, Jean-François, primary, and Bonnet, Dominique, primary

Published
2023
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8. Data from Frequency and Dynamics of Leukemia-Initiating Cells during Short-term Ex Vivo Culture Informs Outcomes in Acute Myeloid Leukemia Patients

Author

Griessinger, Emmanuel, primary, Anjos-Afonso, Fernando, primary, Vargaftig, Jacques, primary, Taussig, David C., primary, Lassailly, François, primary, Prebet, Thomas, primary, Imbert, Véronique, primary, Nebout, Marielle, primary, Vey, Norbert, primary, Chabannon, Christian, primary, Filby, Andrew, primary, Bollet-Quivogne, Frederic, primary, Gribben, John G., primary, Peyron, Jean-François, primary, and Bonnet, Dominique, primary

Published
2023
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9. Supplemental Figures from Frequency and Dynamics of Leukemia-Initiating Cells during Short-term Ex Vivo Culture Informs Outcomes in Acute Myeloid Leukemia Patients

Author

Griessinger, Emmanuel, primary, Anjos-Afonso, Fernando, primary, Vargaftig, Jacques, primary, Taussig, David C., primary, Lassailly, François, primary, Prebet, Thomas, primary, Imbert, Véronique, primary, Nebout, Marielle, primary, Vey, Norbert, primary, Chabannon, Christian, primary, Filby, Andrew, primary, Bollet-Quivogne, Frederic, primary, Gribben, John G., primary, Peyron, Jean-François, primary, and Bonnet, Dominique, primary

Published
2023
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19. Correction: Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment

Author

Caye, Aurélie, primary, Rouault-Pierre, Kevin, additional, Strullu, Marion, additional, Lainey, Elodie, additional, Abarrategi, Ander, additional, Fenneteau, Odile, additional, Arfeuille, Chloé, additional, Osman, Jennifer, additional, Cassinat, Bruno, additional, Pereira, Sabrina, additional, Anjos-Afonso, Fernando, additional, Currie, Erin, additional, Ariza-McNaughton, Linda, additional, Barlogis, Vincent, additional, Dalle, Jean-Hugues, additional, Baruchel, André, additional, Chomienne, Christine, additional, Cavé, Hélène, additional, and Bonnet, Dominique, additional

Published
2020
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20. Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment

Author

Caye, Aurélie, primary, Rouault-Pierre, Kevin, additional, Strullu, Marion, additional, Lainey, Elodie, additional, Abarrategi, Ander, additional, Fenneteau, Odile, additional, Arfeuille, Chloé, additional, Osman, Jennifer, additional, Cassinat, Bruno, additional, Pereira, Sabrina, additional, Anjos-Afonso, Fernando, additional, Currie, Erin, additional, Ariza-McNaughton, Linda, additional, Barlogis, Vincent, additional, Dalle, Jean-Hugues, additional, Baruchel, André, additional, Chomienne, Christine, additional, Cavé, Hélène, additional, and Bonnet, Dominique, additional

Published
2019
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22. Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia

Author

Menendez-Gonzalez, Juan Bautista, primary, Vukovic, Milica, additional, Abdelfattah, Ali, additional, Saleh, Lubaid, additional, Almotiri, Alhomidi, additional, Thomas, Leigh-anne, additional, Agirre-Lizaso, Aloña, additional, Azevedo, Aleksandra, additional, Menezes, Ana Catarina, additional, Tornillo, Giusy, additional, Edkins, Sarah, additional, Kong, Kay, additional, Giles, Peter, additional, Anjos-Afonso, Fernando, additional, Tonks, Alex, additional, Boyd, Ashleigh S., additional, Kranc, Kamil R., additional, and Rodrigues, Neil P., additional

Published
2019
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24. IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in preclinical models of non del5q/5q- AML

Author

Lopez-Millan, Belen, primary, Diaz de la Guardia, Rafael, additional, Roca-Ho, Heleia, additional, Anguita, Eduardo, additional, Islam, Abul B. M. M. K., additional, Romero-Moya, Damia, additional, Prieto, Cristina, additional, Gutierrez-Agüera, Francisco, additional, Bejarano-Garcia, Jose Antonio, additional, Perez-Simon, Jose Antonio, additional, Costales, Paula, additional, Rovira, Montse, additional, Marín, Pedro, additional, Menendez, Silvia, additional, Iglesias, Mar, additional, Fuster, Jose Luis, additional, Urbano-Ispizua, Alvaro, additional, Anjos-Afonso, Fernando, additional, Bueno, Clara, additional, and Menendez, Pablo, additional

Published
2018
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27. Frequency and Dynamics of Leukemia-Initiating Cells during Short-term Ex Vivo Culture Informs Outcomes in Acute Myeloid Leukemia Patients

Author

Griessinger, Emmanuel, Chabannon, Christian, Andrew, Filby, Bollet-Quivogne, Frédéric, John, Gribben G.G., Peyron, Jean François, Bonnet, Dominique, Anjos-Afonso, Fernando, Jacques, Vargaftig, David, Taussig T.C., François, Lassailly, Prebet, Thomas, Véronique, Imbert, Marielle, Nebout, Vey, Norbert, Griessinger, Emmanuel, Chabannon, Christian, Andrew, Filby, Bollet-Quivogne, Frédéric, John, Gribben G.G., Peyron, Jean François, Bonnet, Dominique, Anjos-Afonso, Fernando, Jacques, Vargaftig, David, Taussig T.C., François, Lassailly, Prebet, Thomas, Véronique, Imbert, Marielle, Nebout, and Vey, Norbert

Abstract

Acute myeloid leukemia (AML) is sustained by a subpopulation of rare leukemia-initiating cells (LIC) detected in the xenograft assay by their capacity to self-renew and to generate non-LICs in vivo. The xenotransplantation model captures functional properties of LICs that have clinical prognostic value. However, the long duration of this in vivo assay has hampered its use as a prognostic tool. Here, we show, using an ex vivo coculture system, that intermediate and poor risk AML patient samples at diagnosis have a 5 to 7 times higher frequency of leukemic long-term culture-initiating cells (L-LTC-IC) compared with the good risk group. We defined a fluorescence dilution factor (FDF) parameter that monitors sample proliferation over 1 week and established a strong correlation of this parameter with the L-LTC-IC frequency. A higher FDF was found for poor prognostic AMLs or for samples capable of engrafting NSG mice compared with good risk AMLs or nonengrafters. Importantly, FDF could classify normal karyotype intermediate risk patients into two groups with a significant difference in their overall survival, thus making this nongenetic and non-in vivo approach a new clinically relevant tool for better diagnosis of AML patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016

28. Frequency and Dynamics of Leukemia-Initiating Cells during Short-term Ex Vivo Culture Informs Outcomes in Acute Myeloid Leukemia Patients

Author

Griessinger, Emmanuel, primary, Anjos-Afonso, Fernando, additional, Vargaftig, Jacques, additional, Taussig, David C., additional, Lassailly, François, additional, Prebet, Thomas, additional, Imbert, Véronique, additional, Nebout, Marielle, additional, Vey, Norbert, additional, Chabannon, Christian, additional, Filby, Andrew, additional, Bollet-Quivogne, Frederic, additional, Gribben, John G., additional, Peyron, Jean-François, additional, and Bonnet, Dominique, additional

Published
2016
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29. APOBEC3A is implicated in a novel class of G-to-A mRNA editing in WT1 transcripts

Author

Cancer Research UK, Leukaemia & Lymphoma Research (UK), Niavarani, Ahmadreza, Currie, Erin, Reyal, Yasmin, Anjos-Afonso, Fernando, Horswell, Stuart, Griessinger, Emmanuel, Sardina, Jose Luis, Bonnet, Dominique, Cancer Research UK, Leukaemia & Lymphoma Research (UK), Niavarani, Ahmadreza, Currie, Erin, Reyal, Yasmin, Anjos-Afonso, Fernando, Horswell, Stuart, Griessinger, Emmanuel, Sardina, Jose Luis, and Bonnet, Dominique

Abstract

Classic deamination mRNA changes, including cytidine to uridine (C-to-U) and adenosine to inosine (A-to-I), are important exceptions to the central dogma and lead to significant alterations in gene transcripts and products. Although there are a few reports of non-classic mRNA alterations, as yet there is no molecular explanation for these alternative changes. Wilms Tumor 1 (WT1) mutations and variants are implicated in several diseases, including Wilms tumor and acute myeloid leukemia (AML). We observed two alternative G-to-A changes, namely c.1303G>A and c.1586G>A in cDNA clones and found them to be recurrent in a series of 21 umbilical cord blood mononuclear cell (CBMC) samples studied. Two less conserved U-to-C changes were also observed. These alternative changes were found to be significantly higher in non-progenitor as compared to progenitor CBMCs, while they were found to be absent in a series of AML samples studied, indicating they are targeted, cell type-specific mRNA editing modifications. Since APOBEC/ADAR family members are implicated in RNA/DNA editing, we screened them by RNA-interference (RNAi) for WT1-mRNA changes and observed near complete reversal of WT1 c.1303G>A alteration upon APOBEC3A (A3A) knockdown. The role of A3A in mediating this change was confirmed by A3A overexpression in Fujioka cells, which led to a significant increase in WT1 c.1303G>A mRNA editing. Non-progenitor CBMCs showed correspondingly higher levels of A3A-mRNA and protein as compared to the progenitor ones. To our knowledge, this is the first report of mRNA modifying activity for an APOBEC3 protein and implicates A3A in a novel G-to-A form of editing. These findings open the way to further investigations into the mechanisms of other potential mRNA changes, which will help to redefine the RNA editing paradigm in both health and disease.

Published
2015

32. Declined Presentation

Author

Anjos-Afonso, Fernando, primary, Loizou, Joanna, additional, Bonnet, Dominique, additional, and Behrens, Axel, additional

Published
2014
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33. A Niche-Like Culture System Allowing the Maintenance of Primary Human Acute Myeloid Leukemia-Initiating Cells: A New Tool to Decipher Their Chemoresistance and Self-Renewal Mechanisms

Author

Griessinger, Emmanuel, primary, Anjos-Afonso, Fernando, additional, Pizzitola, Irene, additional, Rouault-Pierre, Kevin, additional, Vargaftig, Jacques, additional, Taussig, David, additional, Gribben, John, additional, Lassailly, François, additional, and Bonnet, Dominique, additional

Published
2014
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36. HIF-2α Protects Human Hematopoietic Stem/Progenitors and Acute Myeloid Leukemic Cells from Apoptosis Induced by Endoplasmic Reticulum Stress

Author

Rouault-Pierre, Kevin, primary, Lopez-Onieva, Lourdes, additional, Foster, Katie, additional, Anjos-Afonso, Fernando, additional, Lamrissi-Garcia, Isabelle, additional, Serrano-Sanchez, Martin, additional, Mitter, Richard, additional, Ivanovic, Zoran, additional, de Verneuil, Hubert, additional, Gribben, John, additional, Taussig, David, additional, Rezvani, Hamid Reza, additional, Mazurier, Frédéric, additional, and Bonnet, Dominique, additional

Published
2013
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37. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells.

Author

Poulin, Lionel, Salio, Mariolina, Griessinger, Emmanuel, Anjos-Afonso, Fernando, Ruscas-Craciun, Ligia Ioana, Chen, Ji-Li, Keller, Anna M, Joffre, Olivier, Zelenay, Santiago, Nye, Emma, Le Moine, Alain, Faure, Florence, Donckier De Donceel, Vincent, Sancho, David, Cerundolo, Vincenzo, Bonnet, Dominique, Reis e Sousa, Caetano, Poulin, Lionel, Salio, Mariolina, Griessinger, Emmanuel, Anjos-Afonso, Fernando, Ruscas-Craciun, Ligia Ioana, Chen, Ji-Li, Keller, Anna M, Joffre, Olivier, Zelenay, Santiago, Nye, Emma, Le Moine, Alain, Faure, Florence, Donckier De Donceel, Vincent, Sancho, David, Cerundolo, Vincenzo, Bonnet, Dominique, and Reis e Sousa, Caetano

Abstract

In mouse, a subset of dendritic cells (DCs) known as CD8alpha+ DCs has emerged as an important player in the regulation of T cell responses and a promising target in vaccination strategies. However, translation into clinical protocols has been hampered by the failure to identify CD8alpha+ DCs in humans. Here, we characterize a population of human DCs that expresses DNGR-1 (CLEC9A) and high levels of BDCA3 and resembles mouse CD8alpha+ DCs in phenotype and function. We describe the presence of such cells in the spleens of humans and humanized mice and report on a protocol to generate them in vitro. Like mouse CD8alpha+ DCs, human DNGR-1+ BDCA3hi DCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8alpha+ DCs) TLR9. DNGR-1+ BDCA3hi DCs respond to poly I:C and agonists of TLR8, but not of TLR7, and produce interleukin (IL)-12 when given innate and T cell-derived signals. Notably, DNGR-1+ BDCA3+ DCs from in vitro cultures efficiently internalize material from dead cells and can cross-present exogenous antigens to CD8+ T cells upon treatment with poly I:C. The characterization of human DNGR-1+ BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2010

41. CD26 Inhibition Can Aid the Homing of Cytokine Activated Mobilized Peripheral Blood (MPB )CD34+ Cells to the Bone Marrow (BM) but a Ligand Dependent Attachment Defect Prevents Their Long Term Retention and Subsequent Engraftment

Author

Kallinikou, Konstantina, primary, Anjos-Afonso, Fernando, additional, Blundell, Michael P, additional, Ings, Stuart J, additional, Kassen, Deepika, additional, Thrasher, Adrian J, additional, Linch, David C, additional, Bonnet, Dominique, additional, and Yong, Kwee, additional

Published
2011
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42. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells

Author

Poulin, Lionel Franz, primary, Salio, Mariolina, additional, Griessinger, Emmanuel, additional, Anjos-Afonso, Fernando, additional, Craciun, Ligia, additional, Chen, Ji-Li, additional, Keller, Anna M., additional, Joffre, Olivier, additional, Zelenay, Santiago, additional, Nye, Emma, additional, Le Moine, Alain, additional, Faure, Florence, additional, Donckier, Vincent, additional, Sancho, David, additional, Cerundolo, Vincenzo, additional, Bonnet, Dominique, additional, and Reis e Sousa, Caetano, additional

Published
2010
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50. Active RHOA favors retention of human hematopoietic stem/progenitor cells in their niche.

Author

Bithiah Grace Jaganathan, Anjos-Afonso, Fernando, Atul Kumar, and Bonnet, Dominique

Subjects
*HEMATOPOIETIC stem cells, *PROGENITOR cells, *BLOOD cells, *CELL cycle, *BONE marrow cells, *STEM cell niches
Abstract

Background: Hematopoietic stem/progenitor cells (HSPCs) maintain the hematopoietic system by balancing their self-renewal and differentiation events. Hematopoietic stem cells also migrate to various sites and interact with their specific microenvironment to maintain the integrity of the system. Rho GTPases have been found to control the migration of hematopoietic cells and other cell types. Although the role of RAC1, RAC2 and CDC42 has been studied, the role of RHOA in human hematopoietic stem cells is unclear. Results: By utilizing constitutively active and dominant negative RHOA, we show that RHOA negatively regulates both in vitro and in vivo migration and dominant negative RHOA significantly increased the migration potential of human HSC/HPCs. Active RHOA expression favors the retention of hematopoietic stem/progenitor cells in the niche rather than migration and was found to lock the cells in the G0 cell cycle phase thereby affecting their long-term self-renewal potential. Conclusion: The current study demonstrates that down-regulation of RHOA might be used to facilitate the migration and homing of hematopoietic stem cells without affecting their long-term repopulating ability. This might be of interest especially for increasing the homing of ex vivo expanded HSPC. [ABSTRACT FROM AUTHOR]

Published
2013

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