11 results on '"Luc Douay"'
Search Results
2. JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma
- Author
-
Laurianne Scourzic, Thomas Mercher, O. De Wever, William Vainchenker, Abdelghani Bouchekioua, P Cervera, Fawzia Louache, Paul Coppo, Luc Douay, Eric Solary, R Nyga, P. Gaulard, Yanyan Zhang, Christian Gespach, A Aline-Fardin, and D Jeziorowska
- Subjects
Adult ,Male ,Cancer Research ,Tumor suppressor gene ,Cell Survival ,T cell ,medicine.disease_cause ,Mice ,Piperidines ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Pyrroles ,Neoplasm Metastasis ,Phosphorylation ,STAT3 ,Protein Kinase Inhibitors ,Aged ,Cell Proliferation ,Neoplasm Staging ,Aged, 80 and over ,Mutation ,biology ,Cell growth ,Janus Kinase 3 ,Hematology ,Middle Aged ,medicine.disease ,Xenograft Model Antitumor Assays ,Tumor Burden ,Lymphoma ,Gene Expression Regulation, Neoplastic ,Lymphoma, Extranodal NK-T-Cell ,Disease Models, Animal ,Pyrimidines ,medicine.anatomical_structure ,Oncology ,Case-Control Studies ,biology.protein ,STAT protein ,Cancer research ,Female ,Janus kinase - Abstract
Extranodal, nasal-type natural killer (NK)/T-cell lymphoma (NKCL) is an aggressive malignancy with poor prognosis in which, usually, signal transducer and activator of transcription 3 (STAT3) is constitutively activated and oncogenic. Here, we demonstrate that STAT3 activation mostly results from constitutive Janus kinase (JAK)3 phosphorylation on tyrosine 980, as observed in three of the four tested NKCL cell lines and in 20 of the 23 NKCL tumor samples under study. In one of the cell lines and in 4 of 19 (21%) NKCL primary tumor samples, constitutive JAK3 activation was related to an acquired mutation (A573V or V722I) in the JAK3 pseudokinase domain. We then show that constitutive activation of the JAK3/STAT3 pathway has a major role in NKCL cell growth and survival and in the invasive phenotype. Indeed, NKCL cell growth was slowed down in vitro by targeting JAK3 with chemical inhibitors or small-interfering RNAs. In a human NKCL xenograft mouse model, tumor growth was significantly delayed by the JAK3 inhibitor CP-690550. Altogether, the constitutive activation of JAK3, which can result from JAK3-activating mutations, is a frequent feature of NKCL that deserves to be tested as a therapeutic target.
- Published
- 2013
3. Genetic hierarchy and temporal variegation in the clonal history of acute myeloid leukaemia
- Author
-
Hannah Moatti, François Delhommeau, Rémi Favier, Mohamad Mohty, Chrystele Bilhou-Nabera, Fawzia Louache, Virginie Joulin, Ruoping Tang, Aline Betems, Elodie Pronier, Florence Lorre, Pascale Flandrin, Ollivier Legrand, Fanny Fava, Christophe Marzac, Pierre Hirsch, Frédéric Féger, Hélène Boutroux, Hayat Mokrani, Luc Douay, Dominique Bories, Yanyan Zhang, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), MYPAC, Université Pierre et Marie Curie - Paris 6 (UPMC), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), CHU Saint-Antoine [AP-HP], Hématologie moléculaire [CHU Mondor], CHU Henri Mondor, Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], and CHU Henri Mondor [Créteil]
- Subjects
0301 basic medicine ,Time Factors ,Myeloid ,Science ,Clone (cell biology) ,General Physics and Astronomy ,Biology ,medicine.disease_cause ,Somatic evolution in cancer ,Article ,General Biochemistry, Genetics and Molecular Biology ,Epigenesis, Genetic ,Clonal Evolution ,Mice ,03 medical and health sciences ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,neoplasms ,Variegation ,Gene Rearrangement ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Mutation ,Multidisciplinary ,Base Sequence ,General Chemistry ,Gene rearrangement ,medicine.disease ,Clone Cells ,Hematopoiesis ,Leukemia, Myeloid, Acute ,Leukemia ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Single-Cell Analysis - Abstract
In acute myeloid leukaemia (AML) initiating pre-leukaemic lesions can be identified through three major hallmarks: their early occurrence in the clone, their persistence at relapse and their ability to initiate multilineage haematopoietic repopulation and leukaemia in vivo. Here we analyse the clonal composition of a series of AML through these characteristics. We find that not only DNMT3A mutations, but also TET2, ASXL1 mutations, core-binding factor and MLL translocations, as well as del(20q) mostly fulfil these criteria. When not eradicated by AML treatments, pre-leukaemic cells with these lesions can re-initiate the leukaemic process at various stages until relapse, with a time-dependent increase in clonal variegation. Based on the nature, order and association of lesions, we delineate recurrent genetic hierarchies of AML. Our data indicate that first lesions, variegation and treatment selection pressure govern the expansion and adaptive behaviour of the malignant clone, shaping AML in a time-dependent manner., Pre-leukaemic clones, together with the propensity to cause disease in mice, are characterized by appearing early in myeloid leukaemia and being found at relapse. Here, the authors identify clones in human samples and find that they are characterized by hierarchically organized genetic lesions, which can be used to track evolution of the disease.
- Published
- 2016
4. Extensive mutational status of genes and clinical outcome in pediatric acute myeloid leukemia
- Author
-
Philippe N, Llopis L, Guy Leverger, Paola Ballerini, Mazingue F, Claude Preudhomme, Lai Jl, Mircea Adam, Myriam Labopin, Christine Perot, Luc Douay, Hélène Lapillonne, Zurawski, Aline Renneville, A. Auvrignon, and Judith Landman-Parker
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Genes, Wilms Tumor ,Adolescent ,Biology ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Mutational status ,Child ,Gene ,Hematology ,Pediatric acute myeloid leukemia ,Infant, Newborn ,Infant ,Cancer ,Histone-Lysine N-Methyltransferase ,medicine.disease ,Leukemia, Myeloid, Acute ,Genes, ras ,fms-Like Tyrosine Kinase 3 ,Child, Preschool ,Multivariate Analysis ,Mutation ,Immunology ,Female ,Myeloid-Lymphoid Leukemia Protein - Abstract
Extensive mutational status of genes and clinical outcome in pediatric acute myeloid leukemia
- Published
- 2009
5. Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells
- Author
-
Laurent Kiger, Michael C. Marden, David Chalmers, Luc Douay, Ladan Kobari, Hélène Lapillonne, Thérèse Cynober, Marie-Catherine Giarratana, and Henri Wajcman
- Subjects
Erythrocytes ,Reticulocytes ,Time Factors ,Stromal cell ,Ultraviolet Rays ,Cellular differentiation ,Cell Culture Techniques ,Biomedical Engineering ,CD34 ,Antigens, CD34 ,Bioengineering ,Cell Separation ,Mice, SCID ,Biology ,Applied Microbiology and Biotechnology ,Hemoglobins ,Mice ,Mice, Inbred NOD ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,Cells, Cultured ,Erythroid Precursor Cells ,Microscopy, Confocal ,Stem Cells ,Cell Differentiation ,Genetic Therapy ,Flow Cytometry ,Hematopoietic Stem Cells ,Coculture Techniques ,Cell biology ,Oxygen ,Haematopoiesis ,Red blood cell ,medicine.anatomical_structure ,Immunology ,Cytokines ,Molecular Medicine ,Erythropoiesis ,Stem cell ,Ex vivo ,Biotechnology - Abstract
We describe here the large-scale ex vivo production of mature human red blood cells (RBCs) from hematopoietic stem cells of diverse origins. By mimicking the marrow microenvironment through the application of cytokines and coculture on stromal cells, we coupled substantial amplification of CD34(+) stem cells (up to 1.95 x 10(6)-fold) with 100% terminal differentiation into fully mature, functional RBCs. These cells survived in nonobese diabetic/severe combined immunodeficient mice, as do native RBCs. Our system for producing 'cultured RBCs' lends itself to a fundamental analysis of erythropoiesis and provides a simple in vitro model for studying important human viral or parasitic infections that target erythroid cells. Further development of large-scale production of cultured RBCs will have implications for gene therapy, blood transfusion and tropical medicine.
- Published
- 2005
6. A novel real-time RT-PCR assay for quantification of OTT-MAL fusion transcript reliable for diagnosis of t(1;22) and minimal residual disease (MRD) detection
- Author
-
A Blaise, E Gatbois, Beatrice Pellegrino, Roland Berger, Thomas Mercher, Christine Perot, Paola Ballerini, Judith Landman-Parker, J van den Akker, Mircea Adam, Luc Douay, and O. Bernard
- Subjects
Cancer Research ,Oncogene Proteins ,RNA-binding protein ,Chromosomal translocation ,Hematology ,Biology ,medicine.disease ,Molecular biology ,Minimal residual disease ,Leukemia ,Real-time polymerase chain reaction ,Oncology ,Fusion transcript ,Antigen ,hemic and lymphatic diseases ,medicine - Abstract
A novel real-time RT-PCR assay for quantification of OTT-MAL fusion transcript reliable for diagnosis of t(1;22) and minimal residual disease (MRD) detection
- Published
- 2003
7. Improved efficiency of remission induction facilitates autologous BMT harvesting and improves overall survival in adults with AML: 108 patients treated at a single institution
- Author
-
Laporte Jp, S Lesage, M Aoudjhane, Norbert-Claude Gorin, L. Fouillard, Albert Najman, P Zunic, M Elloumi, Françoise Isnard, Marcelo F. Lopez, J van den Akker, M Guiguet, N. Cheron, Luc Douay, and Deloux J
- Subjects
Adult ,Amsacrine ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Urology ,Transplantation, Autologous ,chemistry.chemical_compound ,Mafosfamide ,White blood cell ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Survival rate ,Bone Marrow Transplantation ,Etoposide ,Retrospective Studies ,Transplantation ,Chemotherapy ,business.industry ,Remission Induction ,Cytarabine ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,Leukemia ,Treatment Outcome ,medicine.anatomical_structure ,chemistry ,Leukemia, Myeloid ,Acute Disease ,Female ,Bone marrow ,business ,medicine.drug - Abstract
A hundred and eight patients less than 60 years old with de novo acute myeloid leukemia were treated between 1982 and 1994 by protocols including final intensification with a transplant using autologous bone marrow purged by mafosfamide in first remission in the absence of an HLA-matched sibling donor available for allograft. From 1989, we attempted to improve tumor control by using high-dose anthracyclines in induction, by increasing from one to two the number of consolidation courses pre-transplant and by introducing intermediate doses of cytarabine in the first consolidation course. The CR rate was 77% (33/43) before 1989 and 90% (59/65) after 1989 (P = 0.06). Forty-five out of the 59 patients (76%) who achieved CR after 1989 could undergo bone marrow grafting in CR1 vs 16/33 (48%) before 1989 (P = 0.01). In spite of the higher proportion of patients above 50 years after 1989 (32%) toxicity was mild and an adequate graft was obtained more frequently after one collection. The principal factor relating to improvement in graft feasibility was the post-1989 modification of induction and consolidation regimens. This improvement in graft feasibility was associated with a better disease-free survival (DFS) (48 +/- 7% vs 32 +/- 8%, P = 0.04) and overall survival (OS) (53 +/- 6% vs 30 +/- 7%, P = 0.007) at 5 years. By multivariate analysis four factors were associated with overall survival (OS): karyotype, white blood cell count at diagnosis, treatment regimen and bone marrow grafting in CR1. This global approach should be prospectively compared with intensive chemotherapy.
- Published
- 2001
8. Ex vivo expansion of CD34-positive peripheral blood progenitor cells from patients with non-Hodgkin's lymphoma: no evidence of concomitant expansion of contaminating bcl2/JH-positive lymphoma cells
- Author
-
Luc Douay, François M. Lemoine, H Firat, G Andreu, Ming Yao, Marc Lopez, Norbert-Claude Gorin, Stéphane Bouchet, and L. Fouillard
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Cell Culture Techniques ,CD34 ,Antigens, CD34 ,Stem cell factor ,Cell Separation ,Biology ,Transplantation, Autologous ,Immunophenotyping ,hemic and lymphatic diseases ,Biomarkers, Tumor ,medicine ,Humans ,Progenitor cell ,Gene Rearrangement ,Transplantation ,Lymphoma, Non-Hodgkin ,Membrane Proteins ,Hematopoietic stem cell ,Hematology ,Gene rearrangement ,Middle Aged ,Hematopoietic Stem Cells ,Molecular biology ,Haematopoiesis ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,Immunoglobulin Joining Region ,Female ,Stem cell ,Cell Division - Abstract
The aim of the present study was to evaluate the capacity to expand of hematopoietic stem cell (HSC) samples from eight patients with NHL, and to follow in parallel the fate of tumor cells in four of eight samples still containing bcl2/JH+ tumor cells after CD34+ or CD19-/20-/34+ cell selection. The presence of bcl2/JH+ cells was also investigated after expansion in four of eight samples, two of which were bcl2/JH at harvesting and two which were initially bcl2/JH+ but became bcl2/JH (below the level of PCR detection) after cell selection, to assess a possible reappearance of occult tumor cells after expansion culture. We used culture conditions that we previously had established to allow high level expansion of normal precursors, progenitors and LTC-ICs. In this study, particular attention was given to the role of Flt3-ligand, known to favor the growth of B cells. The expansion conditions were: 1.5 x 10(3) cells/ml in serum-free medium containing stem cell factor (SCF), interleukin-3 (IL-3), IL-6, granulocyte-stimulating factor (G-CSF), erythropoietin (Epo) +/- Flt3-ligand (Flt3-L) for 10 days. After culture, total cells, CFU-GMs, BFU-Es and LTC-ICs were expanded to a mean of 833-, 6.6-, 4.6-, and 1.8-fold, respectively with the cocktail of cytokines not including Flt3-L. When Flt3-L was added, the mean expansion values were 1095-, 31-, 15- and three-fold, respectively. Residual bcl2/JH+ cells present in four of eight samples before expansion were not detected after expansion. Similarly, no tumor cells reappeared after expansion of the two samples which had become negative after selection, as well as in the two samples which were bcl2/JH- at harvesting. These results suggest first that ex vivo expansion of hematopoietic stem cells in patients with non-Hodgkin's lymphoma is feasible without incurring the parallel risk of amplifying tumor cells; second, that Flt3-L did not stimulate the growth of tumor cells while it clearly favored the growth of normal progenitors.
- Published
- 2000
9. Cell culture bags allow a large extent of ex vivo expansion of LTC-IC and functional mature cells which can subsequently be frozen: interest for large-scale clinical applications
- Author
-
Marcelo F. Lopez, M-C Giarratana, N. C. Gorin, Ladan Kobari, Tma Neildez Nguyen, Stéphane Bouchet, Luc Douay, H Firat, and Dominique Thierry
- Subjects
Cryopreservation ,Transplantation ,Pathology ,medicine.medical_specialty ,Time Factors ,Granulocytic cells ,Cell Culture Techniques ,Hematopoietic Stem Cell Transplantation ,CD34 ,Hematology ,Biology ,Hematopoietic Stem Cells ,Hematopoietic Stem Cell Mobilization ,Andrology ,Haematopoiesis ,Blood Preservation ,Nucleated cell ,Cell culture ,medicine ,Humans ,Ex vivo expansion ,Progenitor cell ,Stem cell - Abstract
The aim of this study was to evaluate the ex vivo expansion of normal CD34 + cells in gas-permeable polypropylene bags suitable for clinical use. Cells were cultured for 14 days in serum-free medium supplemented with SCF, IL3, IL6, FLT3-1, G-CSF ± MGDF or Epo. The bags supported the expansion of hematopoietic cells in a similar manner to small scale well or flask systems, allowing mean expansions of up to 2193-fold for total nucleated cells, 140-fold for CFU-GM and 66-fold for LTC-IC. Increasing the initial cell concentration from 5 x 10 3 to 1 x 10 5 CD34 + cells/ml induced the production of granulocytic cells with terminal differentiation while simultaneously decreasing the overall extent of expansion of the white blood cells produced. We tested the phagocytic activity and oxidative metabolism of the white blood cells produced. The percentage of phagocytic cells was 39 ± 0.5% in expanded cultures derived from fractions initiated at 5 x 10 3 , 104 or 10 5 cells/ml and 45 ± 6% in cultured cells obtained from starting fractions containing 5 x 10 4 cells/ml, as compared to 58 ± 4% in normal controls. A study of the potential for oxygen-dependent microbe killing showed that the expanded cells produced H 2 O 2 , although in lesser quantities than control cells. We subsequently investigated the possibility of freezing expanded cells. Total cell recovery after thawing was 45 ± 4%, while recoveries of progenitors and stem cells ranged from 65 to 90%, without any influence of the initial cell concentration. This new approach could be of major interest for clinical practice, as it would allow evaluation of the quality of a graft prior to its infusion and employs experimental conditions which meet the criteria for potential clinical use.
- Published
- 1998
10. Negative selection and protection of normal progenitor cells for autografting
- Author
-
Luc Douay
- Subjects
Male ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Bone Marrow Cells ,Transplantation, Autologous ,Humans ,Medicine ,Progenitor cell ,Cytotoxicity ,Bone Marrow Transplantation ,Transplantation ,Chemotherapy ,business.industry ,Bone Marrow Purging ,Hematology ,Amifostine ,Radiation therapy ,medicine.anatomical_structure ,Toxicity ,Cancer research ,Female ,Bone marrow ,business ,Ex vivo ,medicine.drug - Abstract
Autologous bone marrow transplantation (ABMT) after high-dose chemotherapy is recognized as a curative approach to treating hematologic malignancies and some invasive solid tumors. However, tumor cells present in the bone marrow at the time of harvesting are a potential cause for relapse. Ex vivo marrow purging with very high doses of cytotoxic agents has been introduced in an attempt to remove neoplastic cells contaminating the autograft. The procedure, however, has been limited by its high toxicity to normal bone marrow progenitor cells. In their purging procedures, investigators have used agents such as amifostine, originally developed to protect against the effects of radiation and chemotherapy. In this article, the appropriateness of protecting normal cells with amifostine during various purging procedures will be reviewed.
- Published
- 1998
11. In vivo expansion of reinfused autologous peripheral blood stem cells after a myeloablative regimen, as an alternative to ex vivoexpansion pretransplantation: an intriguing observation in a patient autografted twice
- Author
-
Gourmelon P, S Lesage, Albert Najman, Norbert-Claude Gorin, Luc Douay, L. Fouillard, and Laporte Jp
- Subjects
Transplantation ,Pathology ,medicine.medical_specialty ,Regimen ,surgical procedures, operative ,In vivo ,business.industry ,Immunology ,medicine ,Hematology ,Ex vivo expansion ,Peripheral Blood Stem Cells ,business - Abstract
In vivo expansion of reinfused autologous peripheral blood stem cells after a myeloablative regimen, as an alternative to ex vivo expansion pretransplantation: an intriguing observation in a patient autografted twice
- Published
- 1999
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.