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27 results on '"Caye, Aurélie"'

1. Concurrent CDX2 cis-deregulation and UBTF::ATXN7L3 fusion define a novel high-risk subtype of B-cell ALL

Author

Passet, Marie, Kim, Rathana, Gachet, Stéphanie, Sigaux, François, Chaumeil, Julie, Galland, Ava, Sexton, Thomas, Quentin, Samuel, Hernandez, Lucie, Larcher, Lise, Bergugnat, Hugo, Ye, Tao, Karasu, Nezih, Caye, Aurélie, Heizmann, Beate, Duluc, Isabelle, Chevallier, Patrice, Rousselot, Philippe, Huguet, Françoise, Leguay, Thibaut, Hunault, Mathilde, Pflumio, Françoise, Freund, Jean-Noël, Lobry, Camille, Lhéritier, Véronique, Dombret, Hervé, Domon-Dell, Claire, Soulier, Jean, Boissel, Nicolas, and Clappier, Emmanuelle

Published
2022
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3. 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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4. LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia

Author

Helsmoortel, Hetty H., Bresolin, Silvia, Lammens, Tim, Cavé, Hélène, Noellke, Peter, Caye, Aurélie, Ghazavi, Farzaneh, de Vries, Andrica, Hasle, Henrik, Labarque, Veerle, Masetti, Riccardo, Stary, Jan, van den Heuvel-Eibrink, Marry M., Philippé, Jan, Van Roy, Nadine, Benoit, Yves, Speleman, Frank, Niemeyer, Charlotte, Flotho, Christian, Basso, Giuseppe, te Kronnie, Geertruy, Van Vlierberghe, Pieter, and De Moerloose, Barbara

Published
2016
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5. Acute lymphoblastic leukemia in the context of RASopathies

Author

Cavé, Hélène, Caye, Aurélie, Strullu, Marion, Aladjidi, Nathalie, Vignal, Cédric, Ferster, Alice, Méchinaud, Françoise, Domenech, Carine, Pierri, Filomena, Contet, Audrey, Cacheux, Valère, Irving, Julie, Kratz, Christian, Clavel, Jacqueline, and Verloes, Alain

Published
2016
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7. Leukaemic transformation in a 10‐year‐old girl with SRP54 congenital neutropenia.

Author

Calvo, Charlotte, Lainey, Elodie, Caye, Aurélie, Cuccuini, Wendy, Fenneteau, Odile, Yakouben, Karima, Bellanné‐Chantelot, Christine, Baruchel, André, Dalle, Jean‐Hugues, and Leblanc, Thierry

Subjects
EXOCRINE pancreatic insufficiency, NEUTROPENIA, CORD blood transplantation, HEMATOPOIETIC stem cell transplantation, SOMATIC mutation
Abstract

Screening for G-CSF receptor mutations in patients with secondary myeloid or lymphoid transformation of severe congenital neutropenia. In 2018, Bellanné-Chantelot et al. first reported patients with I SRP54 i mutations presenting with severe congenital neutropenia (SCN) and extra-haematopoietic organ dysfunctions close to Shwachman-Diamond syndrome (SDS) phenotypes.1,2 I SRP54 i mutations have been shown as the second most common cause of SCN in the French neutropenia registry.2 Our female patient was diagnosed with SCN at the age of five weeks: full blood cell counts showed profound neutropenia at 100 cells/ l with relative monocytosis at 1400 cells/ l. Systematic screening for immune deficiency and anti-neutrophil autoantibodies was negative. Granulocyte colony-stimulating factor receptor mutations in a patient with acute lymphoblastic leukemia secondary to severe congenital neutropenia. [Extracted from the article]

Published
2022
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8. Juvenile myelomonocytic leukaemia and Noonan syndrome

Author

Strullu, Marion, Caye, Aurélie, Lachenaud, Julie, Cassinat, Bruno, Gazal, Steven, Fenneteau, Odile, Pouvreau, Nathalie, Pereira, Sabrina, Baumann, Clarisse, Contet, Audrey, Sirvent, Nicolas, Méchinaud, Françoise, Guellec, Isabelle, Adjaoud, Dalila, Paillard, Catherine, Alberti, Corinne, Zenker, Martin, Chomienne, Christine, Bertrand, Yves, Baruchel, André, Verloes, Alain, and Cavé, Hélène

Published
2014
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9. Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis

Author

Flex, Elisabetta, Jaiswal, Mamta, Pantaleoni, Francesca, Martinelli, Simone, Strullu, Marion, Fansa, Eyad K., Caye, Aurélie, De Luca, Alessandro, Lepri, Francesca, Dvorsky, Radovan, Pannone, Luca, Paolacci, Stefano, Zhang, Si-Cai, Fodale, Valentina, Bocchinfuso, Gianfranco, Rossi, Cesare, Burkitt-Wright, Emma M.M., Farrotti, Andrea, Stellacci, Emilia, Cecchetti, Serena, Ferese, Rosangela, Bottero, Lisabianca, Castro, Silvana, Fenneteau, Odile, Brethon, Benoît, Sanchez, Massimo, Roberts, Amy E., Yntema, Helger G., Van Der Burgt, Ineke, Cianci, Paola, Bondeson, Marie-Louise, Cristina Digilio, Maria, Zampino, Giuseppe, Kerr, Bronwyn, Aoki, Yoko, Loh, Mignon L., Palleschi, Antonio, Di Schiavi, Elia, Carè, Alessandra, Selicorni, Angelo, Dallapiccola, Bruno, Cirstea, Ion C., Stella, Lorenzo, Zenker, Martin, Gelb, Bruce D., Cavé, Hélène, Ahmadian, Mohammad R., and Tartaglia, Marco

Published
2014
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10. Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients

Author

Donadieu, Jean, Lamant, Marie, Fieschi, Claire, de Fontbrune, Flore Sicre, Caye, Aurélie, Ouachee, Marie, Beaupain, Blandine, Bustamante, Jacinta, Poirel, Hélène, Isidor, Bertrand, Van Den Neste, Eric, Neel, Antoine, Nimubona, Stanislas, Toutain, Fabienne, Barlogis, Vincent, Schleinitz, Nicolas, Leblanc, Thierry, Rohrlich, Pierre, Suarez, Felipe, Ranta, Dana, Chahla, Wadih Abou, Bruno, Bénédicte, Terriou, Louis, Francois, Sylvie, Lioure, Bruno, Ahle, Guido, Bachelerie, Françoise, Preudhomme, Claude, Delabesse, Eric, Cave, Hélène, Bellanné-Chantelot, Christine, Pasquet, Marlène, French GATA2 study group, UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Centre de génétique médicale UCL, and UCL - (SLuc) Service d'hématologie

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Adolescent, GATA2 Deficiency, medicine.medical_treatment, JC virus, Hematopoietic stem cell transplantation, medicine.disease_cause, Infections, Article, 03 medical and health sciences, Young Adult, Germline mutation, Belgium, Internal medicine, Surveys and Questionnaires, Medicine, Humans, Mortality, Child, Immunodeficiency, Germ-Line Mutation, Juvenile myelomonocytic leukemia, business.industry, Progressive multifocal leukoencephalopathy, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Infant, Hematology, Middle Aged, medicine.disease, Bone Marrow Failure, Prognosis, Leukemia, 030104 developmental biology, International Prognostic Scoring System, Child, Preschool, Hematologic Neoplasms, France, business, Infection
Abstract

Heterozygous germline GATA2 mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.

Published
2018

11. 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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12. Concurrent CDX2 cis-deregulation and UBTF::ATXN7L3fusion define a novel high-risk subtype of B-cell ALL

Author

Passet, Marie, Kim, Rathana, Gachet, Stéphanie, Sigaux, François, Chaumeil, Julie, Galland, Ava, Sexton, Thomas, Quentin, Samuel, Hernandez, Lucie, Larcher, Lise, Bergugnat, Hugo, Ye, Tao, Karasu, Nezih, Caye, Aurélie, Heizmann, Beate, Duluc, Isabelle, Chevallier, Patrice, Rousselot, Philippe, Huguet, Françoise, Leguay, Thibaut, Hunault, Mathilde, Pflumio, Françoise, Freund, Jean-Noël, Lobry, Camille, Lhéritier, Véronique, Dombret, Hervé, Domon-Dell, Claire, Soulier, Jean, Boissel, Nicolas, and Clappier, Emmanuelle

Abstract

Oncogenic alterations underlying B-cell acute lymphoblastic leukemia (B-ALL) in adults remain incompletely elucidated. To uncover novel oncogenic drivers, we performed RNA sequencing and whole-genome analyses in a large cohort of unresolved B-ALL. We identified a novel subtype characterized by a distinct gene expression signature and the unique association of 2 genomic microdeletions. The 17q21.31 microdeletion resulted in a UBTF::ATXN7L3fusion transcript encoding a chimeric protein. The 13q12.2 deletion resulted in monoallelic ectopic expression of the homeobox transcription factor CDX2, located 138 kb in cisfrom the deletion. Using 4C-sequencing and CRISPR interference experiments, we elucidated the mechanism of CDX2 cis-deregulation, involving PAN3enhancer hijacking. CDX2/UBTF ALL (n = 26) harbored a distinct pattern of additional alterations including 1q gain and CXCR4activating mutations. Within adult patients with Ph−B-ALL enrolled in GRAALL trials, patients with CDX2/UBTF ALL (n = 17/723, 2.4%) were young (median age, 31 years) and dramatically enriched in females (male/female ratio, 0.2, P= .002). They commonly presented with a pro-B phenotype ALL and moderate blast cell infiltration. They had poor response to treatment including a higher risk of failure to first induction course (19% vs 3%, P= .017) and higher post-induction minimal residual disease (MRD) levels (MRD ≥ 10−4, 93% vs 46%, P< .001). This early resistance to treatment translated into a significantly higher cumulative incidence of relapse (75.0% vs 32.4%, P= .004) in univariate and multivariate analyses. In conclusion, we discovered a novel B-ALL entity defined by the unique combination of CDX2 cis-deregulation and UBTF::ATXN7L3fusion, representing a high-risk disease in young adults.

Published
2022
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13. 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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14. Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients.

Author

UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Centre de génétique médicale UCL, UCL - (SLuc) Service d'hématologie, Donadieu, Jean, Lamant, Marie, Fieschi, Claire, de Fontbrune, Flore Sicre, Caye, Aurélie, Ouachee, Marie, Beaupain, Blandine, Bustamante, Jacinta, Poirel, Hélène, Isidor, Bertrand, Van Den Neste, Eric, Neel, Antoine, Nimubona, Stanislas, Toutain, Fabienne, Barlogis, Vincent, Schleinitz, Nicolas, Leblanc, Thierry, Rohrlich, Pierre, Suarez, Felipe, Ranta, Dana, Chahla, Wadih Abou, Bruno, Bénédicte, Terriou, Louis, Francois, Sylvie, Lioure, Bruno, Ahle, Guido, Bachelerie, Françoise, Preudhomme, Claude, Delabesse, Eric, Cave, Hélène, Bellanné-Chantelot, Christine, Pasquet, Marlène, French GATA2 study group, UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Centre de génétique médicale UCL, UCL - (SLuc) Service d'hématologie, Donadieu, Jean, Lamant, Marie, Fieschi, Claire, de Fontbrune, Flore Sicre, Caye, Aurélie, Ouachee, Marie, Beaupain, Blandine, Bustamante, Jacinta, Poirel, Hélène, Isidor, Bertrand, Van Den Neste, Eric, Neel, Antoine, Nimubona, Stanislas, Toutain, Fabienne, Barlogis, Vincent, Schleinitz, Nicolas, Leblanc, Thierry, Rohrlich, Pierre, Suarez, Felipe, Ranta, Dana, Chahla, Wadih Abou, Bruno, Bénédicte, Terriou, Louis, Francois, Sylvie, Lioure, Bruno, Ahle, Guido, Bachelerie, Françoise, Preudhomme, Claude, Delabesse, Eric, Cave, Hélène, Bellanné-Chantelot, Christine, Pasquet, Marlène, and French GATA2 study group

Abstract

Heterozygous germline mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.

Published
2018

15. Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia

Author

Poglio, Sandrine, primary, Lewandowski, Daniel, additional, Calvo, Julien, additional, Caye, Aurélie, additional, Gros, Audrey, additional, Laharanne, Elodie, additional, Leblanc, Thierry, additional, Landman-Parker, Judith, additional, Baruchel, André, additional, Soulier, Jean, additional, Ballerini, Paola, additional, Clappier, Emmanuelle, additional, and Pflumio, Françoise, additional

Published
2016
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16. Mutations in RIT1 cause Noonan syndrome with possible juvenile myelomonocytic leukemia but are not involved in acute lymphoblastic leukemia

Author

Cavé, Hélène, primary, Caye, Aurélie, additional, Ghedira, Nehla, additional, Capri, Yline, additional, Pouvreau, Nathalie, additional, Fillot, Natacha, additional, Trimouille, Aurélien, additional, Vignal, Cédric, additional, Fenneteau, Odile, additional, Alembik, Yves, additional, Alessandri, Jean-Luc, additional, Blanchet, Patricia, additional, Boute, Odile, additional, Bouvagnet, Patrice, additional, David, Albert, additional, Dieux Coeslier, Anne, additional, Doray, Bérénice, additional, Dulac, Olivier, additional, Drouin-Garraud, Valérie, additional, Gérard, Marion, additional, Héron, Delphine, additional, Isidor, Bertrand, additional, Lacombe, Didier, additional, Lyonnet, Stanislas, additional, Perrin, Laurence, additional, Rio, Marlène, additional, Roume, Joëlle, additional, Sauvion, Sylvie, additional, Toutain, Annick, additional, Vincent-Delorme, Catherine, additional, Willems, Marjorie, additional, Baumann, Clarisse, additional, and Verloes, Alain, additional

Published
2016
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17. Myeloid Dysregulation in a Human Induced Pluripotent Stem Cell Model of PTPN11-Associated Juvenile Myelomonocytic Leukemia

Author

New York State Stem Cell Science, National Institutes of Health (US), Telethon, Mulero-Navarro, Sonia, Sevilla, Ana, Román, Ángel C., Lee, Dung-Fang, D’Souza, Sunita L., Pardo, Sherly, Riess, Ilan, Su, Jie, Cohen, Ninette, Schaniel, Christoph, Rodriguez, Nelson A., Baccarini, Alessia, Brown, Brian D., Cavé, Hélène, Caye, Aurélie, Strullu, Marion, Yalcin, Safak, Park, Christopher Y., Dhandapany, Perundurai S., Yongchao, Ge, Edelmann, Lisa, Bahieg, Sawsan, Raynal, Patrick, Flex, Elisabetta, Tartaglia, Marco, Moore, Kateri A., Lemischka, Ihor R., Gelb, Bruce D., New York State Stem Cell Science, National Institutes of Health (US), Telethon, Mulero-Navarro, Sonia, Sevilla, Ana, Román, Ángel C., Lee, Dung-Fang, D’Souza, Sunita L., Pardo, Sherly, Riess, Ilan, Su, Jie, Cohen, Ninette, Schaniel, Christoph, Rodriguez, Nelson A., Baccarini, Alessia, Brown, Brian D., Cavé, Hélène, Caye, Aurélie, Strullu, Marion, Yalcin, Safak, Park, Christopher Y., Dhandapany, Perundurai S., Yongchao, Ge, Edelmann, Lisa, Bahieg, Sawsan, Raynal, Patrick, Flex, Elisabetta, Tartaglia, Marco, Moore, Kateri A., Lemischka, Ihor R., and Gelb, Bruce D.

Abstract

Somatic PTPN11 mutations cause juvenile myelomonocytic leukemia (JMML). Germline PTPN11 defects cause Noonan syndrome (NS), and specific inherited mutations cause NS/JMML. Here, we report that hematopoietic cells differentiated from human induced pluripotent stem cells (hiPSCs) harboring NS/JMML-causing PTPN11 mutations recapitulated JMML features. hiPSC-derived NS/JMML myeloid cells exhibited increased signaling through STAT5 and upregulation of miR-223 and miR-15a. Similarly, miR-223 and miR-15a were upregulated in 11/19 JMML bone marrow mononuclear cells harboring PTPN11 mutations, but not those without PTPN11 defects. Reducing miR-223’s function in NS/JMML hiPSCs normalized myelogenesis. MicroRNA target gene expression levels were reduced in hiPSC-derived myeloid cells as well as in JMML cells with PTPN11 mutations. Thus, studying an inherited human cancer syndrome with hiPSCs illuminated early oncogenesis prior to the accumulation of secondary genomic alterations, enabling us to discover microRNA dysregulation, establishing a genotype-phenotype association for JMML and providing therapeutic targets.

Published
2015

18. CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol

Author

Ghazavi, Farzaneh, Bertrand, Yves, Minckes, Odile, Costa, Vitor, Ferster, Alina, Mazingue, Françoise, Plat, Geneviève, Plouvier, Emmanuel, Poirée, Marilyne, Uyttebroeck, Anne, van der Werff Ten Bosch, Jutte, Clappier, Emmanuelle, Yakouben, Karima, Helsmoortel, Hetty, Meul, Magali, Van Roy, Nadine, Philippé, Jan, Speleman, Frank, Cavé, Hélène, Van Vlierberghe, Pieter, De Moerloose, Barbara, Lammens, Tim, Suciu, Stefan, Caye, Aurélie, Zegrari, Samira, Bakkus, Marleen, Grarde, Nathalie, Benoît, Yves, Ghazavi, Farzaneh, Bertrand, Yves, Minckes, Odile, Costa, Vitor, Ferster, Alina, Mazingue, Françoise, Plat, Geneviève, Plouvier, Emmanuel, Poirée, Marilyne, Uyttebroeck, Anne, van der Werff Ten Bosch, Jutte, Clappier, Emmanuelle, Yakouben, Karima, Helsmoortel, Hetty, Meul, Magali, Van Roy, Nadine, Philippé, Jan, Speleman, Frank, Cavé, Hélène, Van Vlierberghe, Pieter, De Moerloose, Barbara, Lammens, Tim, Suciu, Stefan, Caye, Aurélie, Zegrari, Samira, Bakkus, Marleen, Grarde, Nathalie, and Benoît, Yves

Abstract

DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% ± 1.2% for patients with deletions versus 83.5% ± 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23-3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2015

19. Juvenile myelomonocytic leukemia displays mutations in components of the RAS pathway and the PRC2 network

Author

Caye, Aurélie, primary, Strullu, Marion, additional, Guidez, Fabien, additional, Cassinat, Bruno, additional, Gazal, Steven, additional, Fenneteau, Odile, additional, Lainey, Elodie, additional, Nouri, Kazem, additional, Nakhaei-Rad, Saeideh, additional, Dvorsky, Radovan, additional, Lachenaud, Julie, additional, Pereira, Sabrina, additional, Vivent, Jocelyne, additional, Verger, Emmanuelle, additional, Vidaud, Dominique, additional, Galambrun, Claire, additional, Picard, Capucine, additional, Petit, Arnaud, additional, Contet, Audrey, additional, Poirée, Marilyne, additional, Sirvent, Nicolas, additional, Méchinaud, Françoise, additional, Adjaoud, Dalila, additional, Paillard, Catherine, additional, Nelken, Brigitte, additional, Reguerre, Yves, additional, Bertrand, Yves, additional, Häussinger, Dieter, additional, Dalle, Jean-Hugues, additional, Ahmadian, Mohammad Reza, additional, Baruchel, André, additional, Chomienne, Christine, additional, and Cavé, Hélène, additional

Published
2015
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20. Myeloid Dysregulation in a Human Induced Pluripotent Stem Cell Model of PTPN11 -Associated Juvenile Myelomonocytic Leukemia

Author

Mulero-Navarro, Sonia, primary, Sevilla, Ana, additional, Roman, Angel C., additional, Lee, Dung-Fang, additional, D’Souza, Sunita L., additional, Pardo, Sherly, additional, Riess, Ilan, additional, Su, Jie, additional, Cohen, Ninette, additional, Schaniel, Christoph, additional, Rodriguez, Nelson A., additional, Baccarini, Alessia, additional, Brown, Brian D., additional, Cavé, Hélène, additional, Caye, Aurélie, additional, Strullu, Marion, additional, Yalcin, Safak, additional, Park, Christopher Y., additional, Dhandapany, Perundurai S., additional, Yongchao, Ge, additional, Edelmann, Lisa, additional, Bahieg, Sawsan, additional, Raynal, Patrick, additional, Flex, Elisabetta, additional, Tartaglia, Marco, additional, Moore, Kateri A., additional, Lemischka, Ihor R., additional, and Gelb, Bruce D., additional

Published
2015
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21. Prognostic Relevance of CD200/Btla Deletions in Pediatric Precursor-B Cell Acute Lymphoblastic Leukemia Treated According to the EORTC-CLG 58951 Protocol

Author

Ghazavi, Farzaneh, primary, Lammens, Tim, additional, Clappier, Emmanuelle, additional, Suciu, Stefan, additional, Caye, Aurélie, additional, Zegrari, Samira, additional, Bakkus, Marleen, additional, Grardel, Nathalie, additional, Benoit, Yves, additional, Bertrand, Yves, additional, Minckes, Odile, additional, Costa, Vitor, additional, Ferster, Alina, additional, Mazingue, Françoise, additional, Plat, Geneviève, additional, Plouvier, Emmanuel, additional, Poirée, Marilyne, additional, Uyttebroeck, Anne, additional, Van der Werff Ten Bosch, Jutte, additional, Helsmoortel, Hetty, additional, Meul, Magali, additional, Van Roy, Nadine, additional, Philippé, Jan, additional, Speleman, Frank, additional, Cavé, Hélène, additional, Van Vlierberghe, Pieter, additional, and De Moerloose, Barbara, additional

Published
2014
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22. ERG Intragenic Deletion Characterizes a Distinct Oncogenic Subtype of B-Cell Precursor Acute Lymphoblastic Leukemia with a Favourable Outcome Despite Frequent IKZF1 Deletions

Author

Clappier, Emmanuelle, primary, Baruchel, André, additional, Rapion, Jérôme, additional, Caye, Aurélie, additional, Khemiri, Ahlème, additional, Hernandez, Lucie, additional, Kabongo, Emmanuelle, additional, Leblanc, Thierry, additional, Yakouben, Karima, additional, Plat, Geneviève, additional, Costa, Vitor, additional, Ferster, Alina, additional, Rossi, Séraphine, additional, Girard, Sandrine, additional, Dastugue, Nicole, additional, Bakkus, Marleen, additional, Suciu, Stefan, additional, Benoit, Yves, additional, Bertrand, Yves, additional, Soulier, Jean, additional, and Cavé, Hélène, additional

Published
2012
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23. LIN28Boverexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia

Author

Helsmoortel, Hetty H., Bresolin, Silvia, Lammens, Tim, Cavé, Hélène, Noellke, Peter, Caye, Aurélie, Ghazavi, Farzaneh, de Vries, Andrica, Hasle, Henrik, Labarque, Veerle, Masetti, Riccardo, Stary, Jan, van den Heuvel-Eibrink, Marry M., Philippé, Jan, Van Roy, Nadine, Benoit, Yves, Speleman, Frank, Niemeyer, Charlotte, Flotho, Christian, Basso, Giuseppe, te Kronnie, Geertruy, Van Vlierberghe, Pieter, and De Moerloose, Barbara

Abstract

Juvenile myelomonocytic leukemia (JMML) is a rare and aggressive stem cell disease of early childhood. RAS activation constitutes the core component of oncogenic signaling. In addition, leukemic blasts in one-fourth of JMML patients present with monosomy 7, and more than half of patients show elevated age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care and results in an event-free survival rate of 50% to 60%, indicating that novel molecular-driven therapeutic options are urgently needed. Using gene expression profiling in a series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28Bexpression. LIN28Boverexpression was significantly correlated with higher HbF levels, whereas patients with monosomy 7 seldom showed enhanced LIN28Bexpression. This finding gives a biological explanation of why patients with monosomy 7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Lastly, high LIN28Bexpression was associated with poor clinical outcome in our JMML patient series but was not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified elevated LIN28Bexpression as a hallmark of a novel fetal-like subgroup in JMML.

Published
2016
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24. ERGIntragenic Deletion Characterizes a Distinct Oncogenic Subtype of B-Cell Precursor Acute Lymphoblastic Leukemia with a Favourable Outcome Despite Frequent IKZF1Deletions

Author

Clappier, Emmanuelle, Baruchel, André, Rapion, Jérôme, Caye, Aurélie, Khemiri, Ahlème, Hernandez, Lucie, Kabongo, Emmanuelle, Leblanc, Thierry, Yakouben, Karima, Plat, Geneviève, Costa, Vitor, Ferster, Alina, Rossi, Séraphine, Girard, Sandrine, Dastugue, Nicole, Bakkus, Marleen, Suciu, Stefan, Benoit, Yves, Bertrand, Yves, Soulier, Jean, and Cavé, Hélène

Abstract

Abstract 121

Published
2012
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25. LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia

Author

Pieter Van Vlierberghe, Christian Flotho, Yves Benoit, Giuseppe Basso, Riccardo Masetti, Hélène Cavé, Jan Stary, Hetty Helsmoortel, Peter Noellke, Nadine Van Roy, Geertruy te Kronnie, Marry M. van den Heuvel-Eibrink, Farzaneh Ghazavi, Frank Speleman, Veerle Labarque, Charlotte M. Niemeyer, Silvia Bresolin, Barbara De Moerloose, Tim Lammens, Henrik Hasle, Aurélie Caye, Andrica C H de Vries, Jan Philippé, Pediatrics, Helsmoortel, Hetty H., Bresolin, Silvia, Lammens, Tim, Cavé, Hélène, Noellke, Peter, Caye, Aurélie, Ghazavi, Farzaneh, De Vries, Andrica, Hasle, Henrik, Labarque, Veerle, Masetti, Riccardo, Stary, Jan, Van Den Heuvel-Eibrink, Marry M., Philippé, Jan, Van Roy, Nadine, Benoit, Yve, Speleman, Frank, Niemeyer, Charlotte, Flotho, Christian, Basso, Giuseppe, Te Kronnie, Geertruy, Van Vlierberghe, Pieter, and De Moerloose, Barbara

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Prognosi, medicine.medical_treatment, Immunology, RNA-Binding Protein, Hematopoietic stem cell transplantation, Biology, Biochemistry, Disease-Free Survival, 03 medical and health sciences, Fetus, Internal medicine, Fetal hemoglobin, medicine, Biomarkers, Tumor, Humans, Fetu, Child, Multivariate Analysi, Fetal Hemoglobin, Hematology, Juvenile myelomonocytic leukemia, Gene Expression Regulation, Leukemic, Hematopoietic Stem Cell Transplantation, RNA-Binding Proteins, Cell Biology, medicine.disease, Prognosis, Leukemia, Haematopoiesis, 030104 developmental biology, Leukemia, Myelomonocytic, Juvenile, Child, Preschool, Multivariate Analysis, Cancer research, Female, Stem cell, Chromosome Deletion, Chromosomes, Human, Pair 7, Human, Chronic myelogenous leukemia
Abstract

Juvenile myelomonocytic leukemia (JMML) is a rare and aggressive stem cell disease of early childhood. RAS activation constitutes the core component of oncogenic signaling. In addition, leukemic blasts in one-fourth of JMML patients present with monosomy 7, and more than half of patients show elevated age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care and results in an event-free survival rate of 50% to 60%, indicating that novel molecular-driven therapeutic options are urgently needed. Using gene expression profiling in a series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression. LIN28B over expression was significantly correlated with higher HbF levels, whereas patients with monosomy 7 seldom showed enhanced LIN28B expression. This finding gives a biological explanation of why patients with monosomy7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7 microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Lastly, high LIN28B expression was associated with poor clinical outcome in our JMML patient series but was not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified elevated LIN28B expression as a hallmark of a novel fetal-like subgroup in JMML.

Published
2016

26. CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol.

Author

Ghazavi F, Clappier E, Lammens T, Suciu S, Caye A, Zegrari S, Bakkus M, Grardel N, Benoit Y, Bertrand Y, Minckes O, Costa V, Ferster A, Mazingue F, Plat G, Plouvier E, Poirée M, Uyttebroeck A, van der Werff-Ten Bosch J, Yakouben K, Helsmoortel H, Meul M, Van Roy N, Philippé J, Speleman F, Cavé H, Van Vlierberghe P, and De Moerloose B

Subjects
Adolescent, Alleles, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Chromosome Breakpoints, Clinical Trials as Topic, Comparative Genomic Hybridization, DNA Copy Number Variations, Female, Gene Frequency, Humans, Infant, Infant, Newborn, Kaplan-Meier Estimate, Male, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma mortality, Prognosis, Recurrence, Antigens, CD genetics, Gene Deletion, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Receptors, Immunologic genetics
Abstract

DNA copy number analysis has been instrumental for the identification of genetic alterations in B-cell precursor acute lymphoblastic leukemia. Notably, some of these genetic defects have been associated with poor treatment outcome and might be relevant for future risk stratification. In this study, we characterized recurrent deletions of CD200 and BTLA genes, mediated by recombination-activating genes, and used breakpoint-specific polymerase chain reaction assay to screen a cohort of 1154 cases of B-cell precursor acute lymphoblastic leukemia uniformly treated according to the EORTC-CLG 58951 protocol. CD200/BTLA deletions were identified in 56 of the patients (4.8%) and were associated with an inferior 8-year event free survival in this treatment protocol [70.2% ± 1.2% for patients with deletions versus 83.5% ± 6.4% for non-deleted cases (hazard ratio 2.02; 95% confidence interval 1.23-3.32; P=0.005)]. Genetically, CD200/BTLA deletions were strongly associated with ETV6-RUNX1-positive leukemias (P<0.0001), but were also identified in patients who did not have any genetic abnormality that is currently used for risk stratification. Within the latter population of patients, the presence of CD200/BTLA deletions was associated with inferior event-free survival and overall survival. Moreover, the multivariate Cox model indicated that these deletions had independent prognostic impact on event-free survival when adjusting for conventional risk criteria. All together, these findings further underscore the rationale for copy number profiling as an important tool for risk stratification in human B-cell precursor acute lymphoblastic leukemia. This trial was registered at www.ClinicalTrials.gov as #NCT00003728., (Copyright© Ferrata Storti Foundation.)

Published
2015
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27. Breakpoint-specific multiplex polymerase chain reaction allows the detection of IKZF1 intragenic deletions and minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia.

Author

Caye A, Beldjord K, Mass-Malo K, Drunat S, Soulier J, Gandemer V, Baruchel A, Bertrand Y, Cavé H, and Clappier E

Subjects
Adolescent, Child, Child, Preschool, Chromosome Breakpoints, Chromosome Mapping, Chromosomes, Human, Pair 7 genetics, Cohort Studies, Comparative Genomic Hybridization, DNA, Intergenic genetics, Female, Genetic Testing methods, Humans, Infant, Male, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Prognosis, Reproducibility of Results, Risk Factors, Sensitivity and Specificity, Ikaros Transcription Factor genetics, Multiplex Polymerase Chain Reaction methods, Neoplasm, Residual genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Sequence Deletion
Abstract

Deletion of the Ikaros (IKZF1) gene is an oncogenic lesion frequently associated with BCR-ABL1-positive acute lymphoblastic leukemias. It is also found in a fraction of BCR-ABL1-negative B-cell precursor acute lymphoblastic leukemias, and early studies showed it was associated with a higher risk of relapse. Therefore, screening tools are needed for evaluation in treatment protocols and possible inclusion in risk stratification. Besides monosomy 7 and large 7p abnormalities encompassing IKZF1, most IKZF1 alterations are short, intragenic deletions. Based on cohorts of patients, we mapped the microdeletion breakpoints and developed a breakpoint-specific fluorescent multiplex polymerase chain reaction that allows detection of recurrent intragenic deletions. This sensitive test could also detect IKZF1 subclonal deletions, whose prognostic significance should be evaluated. Moreover, we show that consensus breakpoint sequences can be used as clonal markers to monitor minimal residual disease. This paper could be useful for translational studies and in clinical management of BCP-ALL.

Published
2013
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