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51. Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with the variant RNF213-, ATIC- and TPM3-ALK fusions is characterized by copy number gain of the rearranged ALK gene

Author

van der Krogt, Jo-Anne, primary, Bempt, Marlies Vanden, additional, Ferreiro, Julio Finalet, additional, Mentens, Nicole, additional, Jacobs, Kris, additional, Pluys, Ursula, additional, Doms, Kathleen, additional, Geerdens, Ellen, additional, Uyttebroeck, Anne, additional, Pierre, Pascal, additional, Michaux, Lucienne, additional, Devos, Timothy, additional, Vandenberghe, Peter, additional, Tousseyn, Thomas, additional, Cools, Jan, additional, and Wlodarska, Iwona, additional

Published
2017
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53. Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, UCL - (MGD) Service d'anatomie pathologique, Van Roosbroeck, Katrien, Ferreiro, Julio Finalet, Tousseyn, Thomas, van der Krogt, Jo-Anne, Michaux, Lucienne, Pienkowska-Grela, Barbara, Théate, Ivan, De Paepe, Pascale, Dierickx, Daan, Doyen, Chantal, Put, Natalie, Cools, Jan, Vandenberghe, Peter, Wlodarska, Iwona, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, UCL - (MGD) Service d'anatomie pathologique, Van Roosbroeck, Katrien, Ferreiro, Julio Finalet, Tousseyn, Thomas, van der Krogt, Jo-Anne, Michaux, Lucienne, Pienkowska-Grela, Barbara, Théate, Ivan, De Paepe, Pascale, Dierickx, Daan, Doyen, Chantal, Put, Natalie, Cools, Jan, Vandenberghe, Peter, and Wlodarska, Iwona

Abstract

The recurrent 9p24.1 aberrations in lymphoid malignancies potentially involving four cancer-related and druggable genes (JAK2, CD274/PDL1, PDCD1LG2/PDL2, and KDM4C/JMJD2Cl) are incompletely characterized. To gain more insight into the anatomy of these abnormalities, at first we studied 9p24.1 alterations in 18 leukemia/lymphoma cases using cytogenetic and molecular techniques. The aberrations comprised structural (nine cases) and numerical (nine cases) alterations. The former lesions were heterogeneous but shared a common breakpoint region of 200 kb downstream of JAK2. The rearrangements predominantly targeted the PDL locus. We have identified five potential partner genes of PDL1/2: PHACTR4 (1p34), N4BP2 (4p14), EEF1A1 (6q13), JAK2 (9p24.1), and IGL (22q11). Interestingly, the cryptic JAK2-PDL1 rearrangement was generated by a microdeletion spanning the 3'JAK2-5'PDL1 region. JAK2 was additionally involved in a cytogenetically cryptic IGH-mediated t(9;14)(p24.1;q32) found in two patients. This rare but likely underestimated rearrangement highlights the essential role of JAK2 in B-cell neoplasms. Cases with amplification of 9p24.1 were diagnosed as primary mediastinal B-cell lymphoma (five cases) and T-cell lymphoma (four cases). The smallest amplified 9p24.1 region was restricted to the JAK2-PDL1/2-RANBP6 interval. In the next step, we screened 200 cases of classical Hodgkin lymphoma by interphase FISH and identified PDL1/2 rearrangement (CIITA- and IGH-negative) in four cases (2%), what is a novel finding. Forty (25%) cases revealed high level amplification of 9p24.1, including four cases with a selective amplification of PDL1/2. Altogether, the majority of 9p24.1 rearrangements occurring in lymphoid malignancies seem to target the programmed death-1 ligands, what potentiates the therapeutic activity of PD-1 blockade in these tumors. © 2016 Wiley Periodicals, Inc.

Published
2016

54. Detection of bone marrow involvement in newly diagnosed post-transplant lymphoproliferative disorder:18F-fluorodeoxyglucose positron emission tomography/computed tomographyversusbone marrow biopsy

Author

Gheysens, Olivier, primary, Thielemans, Sanne, additional, Morscio, Julie, additional, Boeckx, Nancy, additional, Goffin, Karolien E., additional, Deroose, Christophe M., additional, Sagaert, Xavier, additional, Wlodarska, Iwona, additional, Verhoef, Gregor, additional, Dierickx, Daan, additional, and Tousseyn, Thomas, additional

Published
2016
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55. Genomic alterations of theJAK2andPDLloci occur in a broad spectrum of lymphoid malignancies

Author

Van Roosbroeck, Katrien, primary, Ferreiro, Julio Finalet, additional, Tousseyn, Thomas, additional, van der Krogt, Jo-Anne, additional, Michaux, Lucienne, additional, Pienkowska-Grela, Barbara, additional, Theate, Ivan, additional, De Paepe, Pascale, additional, Dierickx, Daan, additional, Doyen, Chantal, additional, Put, Natalie, additional, Cools, Jan, additional, Vandenberghe, Peter, additional, and Wlodarska, Iwona, additional

Published
2016
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56. SEC31A-ALK Fusion Gene in Lung Adenocarcinoma

Author

Kim, Ryong Nam, primary, Choi, Yoon-La, additional, Lee, Mi-Sook, additional, Lira, Maruja E., additional, Mao, Mao, additional, Mann, Derrick, additional, Stahl, Joshua, additional, Licon, Abel, additional, Choi, So Jung, additional, Vrancken, Michael Van, additional, Han, Joungho, additional, Wlodarska, Iwona, additional, and Kim, Jhingook, additional

Published
2016
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57. RPL5 Is a Candidate Tumor Suppressor on 1p22.1 in Multiple Myeloma of Which the Expression Is Linked to Bortezomib Response

Author

Hofman, Isabel JF, primary, van Duin, Mark, additional, Mulligan, George, additional, Geerdens, Ellen, additional, Garelli, Emanuela, additional, Mancini, Cecilia, additional, Lemmens, Heidi, additional, Delforge, Michel, additional, Vandenberghe, Peter, additional, Wlodarska, Iwona, additional, Aspesi, Anna, additional, Michaux, Lucienne, additional, Sonneveld, Pieter, additional, and De Keersmaecker, Kim, additional

Published
2015
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60. Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

Author

Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Labis, Elise, Terré, Christine, Nadal, Nathalie, Laibe, Sophy, Mozziconacci, Marie-Joëlle, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Taviaux, Sylvie, Chapiro, Elise, Nguyen Khac, Florence, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Hematology and Oncology (BCG-HO), Lambert, Frédéric, Vikkula, Miikka, Poirel, Hélène, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, CHU de Liège - Center for Human Genetics, CHU de Nice - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Lille - Center for Human Genetics, CHU de Montpellier - Center for Human Genetics, Groupe Hospitalier Pitié-Salpétrière - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, IPG - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, Institut Paoli-Calmettes - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, Centre Hospitalier de Versailles - Center for Human Genetics, and UCL - SSS/DDUV - Institut de Duve

Subjects
Myeloid, Follicular lymphoma, lcsh:Medicine, Chromosomal translocation, CYTOGENETIC ANALYSIS, TUMOR-SUPPRESSOR GENE, Hematologic Cancers and Related Disorders, Chromosomal Disorders, Chromosome instability, hemic and lymphatic diseases, Molecular Cell Biology, lcsh:Science, In Situ Hybridization, Fluorescence, MYELODYSPLASTIC SYNDROME, Multidisciplinary, medicine.diagnostic_test, Chromosome Biology, NON-HODGKINS-LYMPHOMAS, Chromosomal Deletions and Duplications, Genomics, Hematology, Telomere, DNA-Binding Proteins, medicine.anatomical_structure, Oncology, Chromosomes, Human, Pair 1, Hematologic Neoplasms, Cytogenetic Analysis, Medicine, Research Article, medicine.medical_specialty, Chromosome Structure and Function, Biology, Polymorphism, Single Nucleotide, Cell Line, Cytogenetics, CHROMOSOMAL TRANSLOCATIONS, Complex Karyotype, medicine, Genetics, Cancer Genetics, Humans, Clinical Genetics, Chromosome Aberrations, CHRONIC LYMPHOCYTIC-LEUKEMIA, Breakpoint, lcsh:R, Biology and Life Sciences, Cancers and Neoplasms, Human Genetics, IN-SITU HYBRIDIZATION, medicine.disease, Molecular biology, COPY NUMBER, NEUROBLASTOMA, lcsh:Q, FOLLICULAR LYMPHOMA, Fluorescence in situ hybridization, Transcription Factors
Abstract

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.

Published
2011

61. Non-IG aberrations of FOXP1 in B-cell malignancies lead to an aberrant expression of N-truncated isoforms of FOXP1

Author

UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Rouhigharabaei, Leila, Ferreiro, Julio Finalet, Tousseyn, Thomas, Van Der Krogt, Jo-Anne, Put, Natalie, Haralambieva, Eugenia, Graux, Carlos, Maes, Brigitte, Vicente, Carmen, Vandenberghe, Peter, Cools, Jan, Wlodarska, Iwona, UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Rouhigharabaei, Leila, Ferreiro, Julio Finalet, Tousseyn, Thomas, Van Der Krogt, Jo-Anne, Put, Natalie, Haralambieva, Eugenia, Graux, Carlos, Maes, Brigitte, Vicente, Carmen, Vandenberghe, Peter, Cools, Jan, and Wlodarska, Iwona

Abstract

The transcription factor FOXP1 is implicated in the pathogenesis of B-cell lymphomas through chromosomal translocations involving either immunoglobulin heavy chain (IGH) locus or non-IG sequences. The former translocation, t(3;14)(p13;q32), results in dysregulated expression of FOXP1 juxtaposed with strong regulatory elements of IGH. Thus far, molecular consequences of rare non-IG aberrations of FOXP1 remain undetermined. Here, using molecular cytogenetics and molecular biology studies, we comprehensively analyzed four lymphoma cases with non-IG rearrangements of FOXP1 and compared these with cases harboring t(3;14)(p13;q32)/IGH-FOXP1 and FOXP1-expressing lymphomas with no apparent structural aberrations of the gene. Our study revealed that non-IG rearrangements of FOXP1 are usually acquired during clinical course of various lymphoma subtypes, including diffuse large B cell lymphoma, marginal zone lymphoma and chronic lymphocytic leukemia, and correlate with a poor prognosis. Importantly, these aberrations constantly target the coding region of FOXP1, promiscuously fusing with coding and non-coding gene sequences at various reciprocal breakpoints (2q36, 10q24 and 3q11). The non-IG rearrangements of FOXP1, however, do not generate functional chimeric genes but commonly disrupt the full-length FOXP1 transcript leading to an aberrant expression of N-truncated FOXP1 isoforms (FOXP1NT), as shown by QRT-PCR and Western blot analysis. In contrast, t(3;14)(p13;q32)/IGH-FOXP1 affects the 5′ untranslated region of FOXP1 and results in overexpress the full-length FOXP1 protein (FOXP1FL). RNA-sequencing of a few lymphoma cases expressing FOXP1NT and FOXP1FL detected neither FOXP1-related fusions nor FOXP1 mutations. Further bioinformatic analysis of RNA-sequencing data retrieved a set of genes, which may comprise direct or non-direct targets of FOXP1NT, potentially implicated in disease progression. In summary, our findings point to a dual mechanism through which FOXP1 is impli

Published
2014

62. Non-Invasive Detection of Genomic Imbalances in Hodgkin/Reed-Sternberg Cells in Early and Advanced Stage Hodgkin Lymphoma By Sequencing of Circulating Cell-Free DNA

Author

Vandenberghe, Peter, primary, Wlodarska, Iwona, additional, Tousseyn, Thomas, additional, Dehaspe, Luc, additional, Dierickx, Daan, additional, Verheecke, Magali, additional, Uyttebroeck, Anne, additional, Bechter, Oliver, additional, Delforge, Michel, additional, Vandecaveye, Vincent, additional, Brison, Nathalie, additional, Verhoef, Gregor EG, additional, Legius, Eric, additional, Amant, Frederic, additional, and Vermeesch, Joris R, additional

Published
2014
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64. Integrative Genomic and Transcriptomic Analysis Identified Candidate Genes Implicated in the Pathogenesis of Hepatosplenic T-Cell Lymphoma

Author

Finalet Ferreiro, Julio, primary, Rouhigharabaei, Leila, additional, Urbankova, Helena, additional, van der Krogt, Jo-Anne, additional, Michaux, Lucienne, additional, Shetty, Shashirekha, additional, Krenacs, Laszlo, additional, Tousseyn, Thomas, additional, De Paepe, Pascale, additional, Uyttebroeck, Anne, additional, Verhoef, Gregor, additional, Taghon, Tom, additional, Vandenberghe, Peter, additional, Cools, Jan, additional, and Wlodarska, Iwona, additional

Published
2014
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66. Non-IG Aberrations of FOXP1 in B-Cell Malignancies Lead to an Aberrant Expression of N-Truncated Isoforms of FOXP1

Author

Rouhigharabaei, Leila, primary, Finalet Ferreiro, Julio, additional, Tousseyn, Thomas, additional, van der Krogt, Jo-Anne, additional, Put, Natalie, additional, Haralambieva, Eugenia, additional, Graux, Carlos, additional, Maes, Brigitte, additional, Vicente, Carmen, additional, Vandenberghe, Peter, additional, Cools, Jan, additional, and Wlodarska, Iwona, additional

Published
2014
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67. BMI1, the polycomb-group gene, is recurrently targeted by genomic rearrangements in progressive B-cell leukemia/lymphoma

Author

UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Rouhigharabaei, Leila, Ferreiro, Julio Finalet, Put, Natalie, Michaux, Lucienne, Tousseyn, Thomas, Lefebvre, Christine, Gardiner, Anne, De Kelver, Wim, Demuynck, Hilde, Verschuere, Johan, Théate, Ivan, Vicente, Carmen, Vandenberghe, Peter, Cools, Jan, Wlodarska, Iwona, UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Rouhigharabaei, Leila, Ferreiro, Julio Finalet, Put, Natalie, Michaux, Lucienne, Tousseyn, Thomas, Lefebvre, Christine, Gardiner, Anne, De Kelver, Wim, Demuynck, Hilde, Verschuere, Johan, Théate, Ivan, Vicente, Carmen, Vandenberghe, Peter, Cools, Jan, and Wlodarska, Iwona

Abstract

BMI1, a Polycomb-group gene located at 10p12.2, is implicated in the pathogenesis of a variety of tumors. However, the genetic molecular mechanisms underlying its aberrant expression in cancer cells remain largely unknown. In this study, we show that BMI1 is recurrently targeted by chromosomal aberrations in B-cell leukemia/lymphoma. We identified a novel t(10;14)(p12;q32)/IGH-BMI1 rearrangement and its IGL variant in six cases of chronic lymphocytic leukemia (CLL) and found that these aberrations were consistently acquired at time of disease progression and high grade transformation of leukemia (Richter syndrome). The IG-BMI1 translocations were not associated with any particular molecular subtype of CLL and the leukemias were negative for common mutations of NOTCH1 and TP53, known to increase a risk of progression and transformation in CLL. In addition, using FISH and SNP array analysis, we identified a wide range of BMI1-involving 10p12 lesions in 17 cases of mantle cell lymphoma (MCL). These aberrations included various balanced and unbalanced structural abnormalities and very frequently but not exclusively, were associated with gain of the BMI1 locus and loss of the 10p terminal sequences. These findings point to genomic instability at the 10p region in MCL which likely promotes rearrangements and deregulation of BMI1. Our findings are in line with previously published observations correlating overexpression of BMI1 with tumor progression and chemoresistance. In summary, our study provides new insights into genetic molecular mechanisms underlying aberrant expression of BMI1 in lymphoma and documents its contribution in the pathogenesis of Richter syndrome and MCL.

Published
2013

68. Comprehensive Analysis of Transcriptome Variation Uncovers Known and Novel Driver Events in T-Cell Acute Lymphoblastic Leukemia

Author

Kalender Atak, Zeynep, primary, Gianfelici, Valentina, additional, Hulselmans, Gert, additional, De Keersmaecker, Kim, additional, Devasia, Arun George, additional, Geerdens, Ellen, additional, Mentens, Nicole, additional, Chiaretti, Sabina, additional, Durinck, Kaat, additional, Uyttebroeck, Anne, additional, Vandenberghe, Peter, additional, Wlodarska, Iwona, additional, Cloos, Jacqueline, additional, Foà, Robin, additional, Speleman, Frank, additional, Cools, Jan, additional, and Aerts, Stein, additional

Published
2013
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69. PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

Author

UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Montano Almendras, Carmen Patricia, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO), Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Auger, Nathalie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Roche-Lestienne, Catherine, Latinne, Dominique, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Montano Almendras, Carmen Patricia, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO), Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Auger, Nathalie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Roche-Lestienne, Catherine, Latinne, Dominique, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, and Poirel, Hélène

Abstract

The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34(+) cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies.

Published
2012

70. Rearrangement of NOTCH1 or BCL3 can independently trigger progression of CLL

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, De Keersmaecker, Kim, Michaux, Lucienne, Bosly, André, Graux, Carlos, Ferreiro, Julio Finalet, Vandenberghe, Peter, Cools, Jan, Wlodarska, Iwona, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, De Keersmaecker, Kim, Michaux, Lucienne, Bosly, André, Graux, Carlos, Ferreiro, Julio Finalet, Vandenberghe, Peter, Cools, Jan, and Wlodarska, Iwona

Published
2012

71. Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course

Author

UCL - SSS/DDUV - Institut de Duve, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, Put, Natalie, Van Roosbroeck, Katrien, Konings, Peter, Meeus, Peter, Brusselmans, Caroline, Rack, Katrina, Gervais, Carine, Nguyen-Khac, Florence, Chapiro, Elise, Radford-Weiss, Isabelle, Struski, Stéphanie, Dastugue, Nicole, Gachard, Nathalie, Lefebvre, Christine, Barin, Carole, Eclache, Virginie, Fert-Ferrer, Sandra, Laibe, Sophy, Mozziconacci, Marie-Joëlle, Quilichini, Benoît, Poirel, Hélène, Wlodarska, Iwona, Hagemeijer, Anne, Moreau, Yves, Vandenberghe, Peter, Michaux, Lucienne, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, Put, Natalie, Van Roosbroeck, Katrien, Konings, Peter, Meeus, Peter, Brusselmans, Caroline, Rack, Katrina, Gervais, Carine, Nguyen-Khac, Florence, Chapiro, Elise, Radford-Weiss, Isabelle, Struski, Stéphanie, Dastugue, Nicole, Gachard, Nathalie, Lefebvre, Christine, Barin, Carole, Eclache, Virginie, Fert-Ferrer, Sandra, Laibe, Sophy, Mozziconacci, Marie-Joëlle, Quilichini, Benoît, Poirel, Hélène, Wlodarska, Iwona, Hagemeijer, Anne, Moreau, Yves, Vandenberghe, Peter, and Michaux, Lucienne

Abstract

Translocations involving MYC are rare in chronic lymphocytic leukemia (CLL), and up to now, their prognostic significance remains unclear. We report the characteristics of 21 patients with CLL and nine patients with prolymphocytic leukemia (PLL), diagnosed in multiple centers (n = 13), which showed an MYC translocation demonstrated by fluorescence in situ hybridization. The prevalence was estimated to be <1%. Advanced age and male predominance were observed. Morphological analysis frequently revealed the presence of prolymphocytes. A typical "CLL-immunophenotype" was found in four of nine cases with PLL. Moreover, CD5 and CD23 were frequently expressed in PLL. The latter findings are atypical for PLL and may suggest transformation or progression of an underlying CLL. MYC translocations were frequently observed with concomitant adverse cytogenetic markers, such as del(11q) (n = 8/30) and/or del(17p)/monosomy 17 (n = 7/30). In addition, the presence of unbalanced translocations (n = 24 in 13/30 cases) and complex karyotype (n = 16/30) were frequent in cases with MYC translocations. Altogether, del(17p)/monosomy 17, del(11q), and/or complex karyotype were observed in 22 of 30 patients. Survival outcome was poor: the median time to treatment was only 5 months, and overall survival (OS) from clinical diagnosis and from genetic detection was 71 and 19 months, respectively. In conclusion, CLL/PLL with MYC translocations is a rare entity, which seems to be associated with adverse prognostic features and unfavorable outcome.

Published
2012

72. Recurrent breakpoints in 14q32.13/TCL1A region in mature B-cell neoplasms with villous lymphocytes

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'hématologie, Urbankova, Helena, Baens, Mathijs, Michaux, Lucienne, Tousseyn, Thomas, Rack, Katrina, Katrincsakova, Beata, Ferreiro, Julio Finalet, van Loo, Peter, de Kelver, Wim, Dierickx, Daan, Demuynck, Hilde, Delannoy, André, Verschuere, Johan, Jarošová, Marie, de Wolf-Peeters, Chris, Vandenberghe, Peter, Wlodarska, Iwona, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'hématologie, Urbankova, Helena, Baens, Mathijs, Michaux, Lucienne, Tousseyn, Thomas, Rack, Katrina, Katrincsakova, Beata, Ferreiro, Julio Finalet, van Loo, Peter, de Kelver, Wim, Dierickx, Daan, Demuynck, Hilde, Delannoy, André, Verschuere, Johan, Jarošová, Marie, de Wolf-Peeters, Chris, Vandenberghe, Peter, and Wlodarska, Iwona

Abstract

The genetic background of mature B-cell neoplasms with villous lymphocytes is poorly understood. We identified a novel breakpoint region at 14q32.13 that was rearranged together with IGH/14q32.33 in four cases of BRAF/V600E-negative leukemia/lymphoma with villous lymphocytes carrying either t(14;14)(q32.13;q32.33) (three patients) or del(14)(q32.13q32.33) (one patient). The 14q32.13 breakpoints were mapped by fluorescence in situ hybridization (FISH) in the region harboring the TCL1A/TCL1B/TCL6 genes, known to be affected by TCRA/D-mediated t(14;14)(q11;q32)/inv(14)(q11q32) occurring in T-cell leukemia/lymphoma. To identify the target of t(14;14)(q32.13; q32.33) and del(14)(q32.13q32.33), quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 25 candidate genes located centromerically and telomerically to the 14q32.13 breakpoint was performed. Any of the analyzed genes was commonly overexpressed in the presented cases. Of note, up-regulated transcription of TCL1A was observed in two cases. In summary, we provide evidence that IGH-mediated chromosomal aberrations affecting the 14q32.13/TCL1A-TCL6 region are recurrent in mature B-cell neoplasms with villous lymphocytes. Despite extensive qRT-PCR studies, molecular consequences of these novel aberrations remain elusive.

Published
2012

73. PRDM16 alterations are frequently encountered in secondary acute myeloid leukemias after chemotherapy and/or radiation therapy

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Institut Paoli-Calmettes, Marseille - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, CHU de Liège - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Nice - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, IPG, Gosselies - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, CHU Timone, Marseille - Center for Human Genetics, Hôpital Arnaud de Villeneuve, Montpellier - Center for Human Genetics, Institut Gustave Roussy, Villejuif - Center for Human Genetics, CHU de Lille - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Auger, Nathalie, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, 13th Annual Meeting of the Belgian Society of Medical Oncology, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Institut Paoli-Calmettes, Marseille - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, CHU de Liège - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Nice - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, IPG, Gosselies - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, CHU Timone, Marseille - Center for Human Genetics, Hôpital Arnaud de Villeneuve, Montpellier - Center for Human Genetics, Institut Gustave Roussy, Villejuif - Center for Human Genetics, CHU de Lille - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Auger, Nathalie, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, and 13th Annual Meeting of the Belgian Society of Medical Oncology

Published
2011

74. PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Institut Paoli-Calmettes, Marseille - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, CHU de Liège - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Nice - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, CHU Timone, Marseille - Center for Human Genetics, Institut Gustave Roussy, Villejuif - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Nadal, Nathalie, Lafage, Marina, Auger, Nathalie, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, Annual Meeting of the American Society of Clinical Oncology (ASCO), UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Institut Paoli-Calmettes, Marseille - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, CHU de Liège - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Nice - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, CHU Timone, Marseille - Center for Human Genetics, Institut Gustave Roussy, Villejuif - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Nadal, Nathalie, Lafage, Marina, Auger, Nathalie, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, and Annual Meeting of the American Society of Clinical Oncology (ASCO)

Published
2011

75. Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, CHU de Liège - Center for Human Genetics, CHU de Nice - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Lille - Center for Human Genetics, CHU de Montpellier - Center for Human Genetics, Groupe Hospitalier Pitié-Salpétrière - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, IPG - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, Institut Paoli-Calmettes - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, Centre Hospitalier de Versailles - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Labis, Elise, Terré, Christine, Nadal, Nathalie, Laibe, Sophy, Mozziconacci, Marie-Joëlle, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Taviaux, Sylvie, Chapiro, Elise, Nguyen Khac, Florence, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Hematology and Oncology (BCG-HO), Lambert, Frédéric, Vikkula, Miikka, Poirel, Hélène, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, CHU de Liège - Center for Human Genetics, CHU de Nice - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Lille - Center for Human Genetics, CHU de Montpellier - Center for Human Genetics, Groupe Hospitalier Pitié-Salpétrière - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, IPG - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, Institut Paoli-Calmettes - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, Centre Hospitalier de Versailles - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Labis, Elise, Terré, Christine, Nadal, Nathalie, Laibe, Sophy, Mozziconacci, Marie-Joëlle, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Taviaux, Sylvie, Chapiro, Elise, Nguyen Khac, Florence, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Hematology and Oncology (BCG-HO), Lambert, Frédéric, Vikkula, Miikka, and Poirel, Hélène

Abstract

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.

Published
2011

76. Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies.

Author

UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Lambert, Frédéric, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Labis, Elise, Taviaux, Sylvie, Chapiro, Elise, Nguyen-Khac, Florence, Khac, Florence Nguyen, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Nadal, Nathalie, Terré, Christine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Vikkula, Miikka, Poirel, Hélène, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Lambert, Frédéric, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Labis, Elise, Taviaux, Sylvie, Chapiro, Elise, Nguyen-Khac, Florence, Khac, Florence Nguyen, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Nadal, Nathalie, Terré, Christine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Vikkula, Miikka, and Poirel, Hélène

Abstract

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.

Published
2011

77. Differential expression of NF-kappa B target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism

Author

UCL, Hamoudi, R. A., Appert, A., Ye, H., Ruskone-Fourmestraux, A., Streubel, B., Chott, A., Raderer, M., Gong, L., Wlodarska, Iwona, De Wolf-Peeters, C., MacLennan, K. A., de Leval, L., Isaacson, P. G., Du, M-Q, UCL, Hamoudi, R. A., Appert, A., Ye, H., Ruskone-Fourmestraux, A., Streubel, B., Chott, A., Raderer, M., Gong, L., Wlodarska, Iwona, De Wolf-Peeters, C., MacLennan, K. A., de Leval, L., Isaacson, P. G., and Du, M-Q

Abstract

Mucosa-associated lymphoid tissue (MALT) lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the nuclear factor (NF)-kappa B pathway. Gastric MALT lymphomas harboring such translocations usually do not respond to Helicobacter pylori eradication, while most of those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 21 MALT lymphomas (13 translocation-positive, 8 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-kappa B target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions have shown that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-kappa B target genes, particularly toll like receptor (TLR)6, chemokine, CC motif, receptor (CCR)2, cluster of differentiation (CD) 69 and B-cell CLL/lymphoma (BCL)2, while translocation-negative cases were featured by active inflammatory and immune responses, such as interleukin-8, CD86, CD28 and inducible T-cell costimulator (ICOS). Separate analyses of the genes differentially expressed between translocation-positive and -negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10-mediated NF-kappa B activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors. Leukemia (2010) 24, 1487-1497; doi:10.1038/leu.2010.118; published online 3 June 2010

Published
2010

78. The t(14;20)(q32;q12): a rare cytogenetic change in multiple myeloma associated with poor outcome

Author

UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Vekemans, Marie-Christiane, Michaux, Lucienne, Lemmens, Heidi, Delforge, Michel, Doyen, Chantal, Pierre, Pascal, Demuynck, Hilde, Bries, Greet, Lemmens, Jan, Meeus, Peter, Straetmans, Nicole, Bauwens, Deborah, Vidrequin, Sebastien, Rack, Katrina, Vandenberghe, Peter, Wlodarska, Iwona, UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Vekemans, Marie-Christiane, Michaux, Lucienne, Lemmens, Heidi, Delforge, Michel, Doyen, Chantal, Pierre, Pascal, Demuynck, Hilde, Bries, Greet, Lemmens, Jan, Meeus, Peter, Straetmans, Nicole, Bauwens, Deborah, Vidrequin, Sebastien, Rack, Katrina, Vandenberghe, Peter, and Wlodarska, Iwona

Published
2010

79. Non-ig Mediated Aberrations of Foxp1 in Human B Cell Lymphoma

Author

UCL - Autre, Rouhigharabaei, L., Tousseyn, Thomas, Haralambieva, E., Maes, B., Vicente, C., Vandenberghe, Peter, de Wolf-Peeters, C., Cools, Jan, Wlodarska, Iwona, 15th Annual Meeting of the European-Hematology-Association, UCL - Autre, Rouhigharabaei, L., Tousseyn, Thomas, Haralambieva, E., Maes, B., Vicente, C., Vandenberghe, Peter, de Wolf-Peeters, C., Cools, Jan, Wlodarska, Iwona, and 15th Annual Meeting of the European-Hematology-Association

Abstract

Background. The FOXP1 forkhead transcription factor is targeted by rare but recurrent translocations in B-NHL, particularly marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). The most common is IGH-mediated t(3;14)(p14;q32) resulting in deregulation of FOXP1 transcription by regulatory sequences of IGH. Several translocations of FOXP1 involving non-IG loci have been described, but remain uncharacterized at the molecular level. Aims. This study aimed at genetic and molecular characterization of non-IG FOXP1 aberrations identified in 4 lymphoma cases. Methods. FISH with a panel of BAC probes was applied to map the affected breakpoints at 3p14/FOXP1 and 2q36, 3q11-q13 and 10q24. Expression of FOXP1 mRNA was analyzed by quantitative RT-PCR (QRT-PCR) with primers specific for exons 5-6, 7-8, 11-12, 14-15 and 17-18. Expression of FOXP1 protein was demonstrated by immunohistochemistry (IHC) with the JC12 antibody. Results. All 4 cases showed an aberrant expression of FOXP1 protein by IHC. Three of them displayed various 3p14 aberrations including t(2;3)(q36;p14) (C1) (MZL), inv(3)(p14;q11) (C2) (MZL) and t(3;10)(p14;q24) (C3) (CLL in Richter transformation). In one case of DLBCL (C4) a non-IG t(FOXP1) was detected by interphase FISH. In contrast to lymphomas with t(3;14) showing the 3p14 breakpoints in the 5’end of FOXP1, all cases with non-IG FOXP1 rearrangements displayed breakpoints in the 3’end of the gene. The reciprocal breakpoints were mapped within AP1S3 at 2q36 (C1), in a region at 3q11 lacking known genes (C2) and close to NFKB2 at 10q24 (C3). In C1, AP1S3 has an opposite transcriptional orientation to FOXP1, which precludes the role of its 5’ promoter in deregulation of FOXP1. Also the mechanism of FOXP1 overexpression in C2 with inv(3) affecting no known gene locus at 3q11 remains unknown. To check the hypothesis that non-IG translocations of FOXP1 result in an aberrant expression of variant FOXP1 transcripts, we performed exon-specific QRT

Published
2010

80. PRDM16 is frequently rearranged with various partner genes in myeloid malignancies with 1p36 alterations

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, KULeuven - Department of Human Genetics, Institut Paoli-Calmettes - Départements d'Oncologie Moléculaire et de BioPathologie, Hôpital Jeanne de Flandre - Unité Inserm U524, CHU de Nice - Service de Génétique, CHU de Liège - Service de Génétique, UZ Gent - Centrum for Medische Genetica, CHU de Toulouse - Service de Génétique, CHU de Montpellier - Service de Génétique, CHU de Saint-Etienne - Service de Génétique, CHU de Nantes - Service de Génétique, CHU de Bordeaux - Service de Génétique, IPG - Service de Génétique, CHU de Dijon - Service de Génétique, Hôpital de la Pitié-Salpêtrière - Service de Génétique, Institut Gustave Roussy - Service de Génétique, CHU Timone - Laboratoire de Cytogénétique Onco-hématologique, Centre Hospitalier de Versailles - Service de Génétique, Centre Hospitalier de Besançon - Service de Génétique, Centre Hospitalier Lyon Sud - Service de Génétique, CHU de Genève - Service de Génétique, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Wlodarska, Iwona, Mozziconacci, Marie-Joëlle, Roche-Lestienne, Catherine, Raynaud, Sophie, Herens, Christian, Speleman, Frank, Dastugue, Nicole, Taviaux, Sylvie, Nadal, Nathalie, Talmant, Pascaline, Lippert, Eric, Rack, Katrina, Mugneret, Francine, Nguyen-Khac, Florence, Auger, Nathalie, Lafage, Marina, Terré, Christine, Collonge-Rame, Marie-Agnès, Tigaud, Isabelle, Cabrol, Christine, Libouton, Jeanne-Marie, Poirel, Hélène, European Human Genetics Conference, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, KULeuven - Department of Human Genetics, Institut Paoli-Calmettes - Départements d'Oncologie Moléculaire et de BioPathologie, Hôpital Jeanne de Flandre - Unité Inserm U524, CHU de Nice - Service de Génétique, CHU de Liège - Service de Génétique, UZ Gent - Centrum for Medische Genetica, CHU de Toulouse - Service de Génétique, CHU de Montpellier - Service de Génétique, CHU de Saint-Etienne - Service de Génétique, CHU de Nantes - Service de Génétique, CHU de Bordeaux - Service de Génétique, IPG - Service de Génétique, CHU de Dijon - Service de Génétique, Hôpital de la Pitié-Salpêtrière - Service de Génétique, Institut Gustave Roussy - Service de Génétique, CHU Timone - Laboratoire de Cytogénétique Onco-hématologique, Centre Hospitalier de Versailles - Service de Génétique, Centre Hospitalier de Besançon - Service de Génétique, Centre Hospitalier Lyon Sud - Service de Génétique, CHU de Genève - Service de Génétique, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Wlodarska, Iwona, Mozziconacci, Marie-Joëlle, Roche-Lestienne, Catherine, Raynaud, Sophie, Herens, Christian, Speleman, Frank, Dastugue, Nicole, Taviaux, Sylvie, Nadal, Nathalie, Talmant, Pascaline, Lippert, Eric, Rack, Katrina, Mugneret, Francine, Nguyen-Khac, Florence, Auger, Nathalie, Lafage, Marina, Terré, Christine, Collonge-Rame, Marie-Agnès, Tigaud, Isabelle, Cabrol, Christine, Libouton, Jeanne-Marie, Poirel, Hélène, and European Human Genetics Conference

Published
2010

81. BMI1, the Polycomb-Group Gene, Is Recurrently Targeted by Genomic Rearrangements in Progressive B-Cell Leukemia/Lymphoma.

Author

UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Rouhi, Leila, Théate, Ivan, Michaux, Lucienne, Put, Natalie, Tousseyn, Thomas, Ferreiro, Julio Finalet, De Kelver, Wim, Demuynck, Hilde, Verschuere, Johan, Vicente, Carmen, De Wolf-Peeters, Chris, Vandenberghe, Peter, Cools, Jan, Wlodarska, Iwona, 51st Annual Meeting of the American-Society-of-Hematology, UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Rouhi, Leila, Théate, Ivan, Michaux, Lucienne, Put, Natalie, Tousseyn, Thomas, Ferreiro, Julio Finalet, De Kelver, Wim, Demuynck, Hilde, Verschuere, Johan, Vicente, Carmen, De Wolf-Peeters, Chris, Vandenberghe, Peter, Cools, Jan, Wlodarska, Iwona, and 51st Annual Meeting of the American-Society-of-Hematology

Published
2009

82. JAK2 Rearrangements, Including the Novel SEC31A-JAK2 Fusion, Are Recurrent in Classical Hodgkin Lymphoma

Author

UCL - Autre, Van Roosbroeck, Katrien, Cox, Luk, Lahortiga, Idoya, Gielen, Olga, Tousseyn, Thomas, Cauwelier, Barbara, De Paepe, Pascale, Vandenberghe, Peter, Marynen, Peter, De Wolf-Peeters, Chris, Cools, Jan, Wlodarska, Iwona, 51st Annual Meeting of the American-Society-of-Hematology, UCL - Autre, Van Roosbroeck, Katrien, Cox, Luk, Lahortiga, Idoya, Gielen, Olga, Tousseyn, Thomas, Cauwelier, Barbara, De Paepe, Pascale, Vandenberghe, Peter, Marynen, Peter, De Wolf-Peeters, Chris, Cools, Jan, Wlodarska, Iwona, and 51st Annual Meeting of the American-Society-of-Hematology

Published
2009

83. Cll With T(14;18): a Distinct Disease?

Author

UCL - MD/BICL - Département de biochimie et de biologie cellulaire, UCL - SC/CHIM - Département de chimie, UCL - MD/MINT - Département de médecine interne, UCL - (MGD) Laboratoire de biologie clinique, UCL - (MGD) Service d'hématologie, Put, Natalie, Meeus, Peter, Chatelain, Bernard, Stul, M., Boeckx, N., Graux, Carlos, Bries, G., Doyen, Chantal, Dubois, Christine, Marichal, S., Pierre, Patrick, Van Hoof, A., Verschuere, J., Harlet, L., Wlodarska, Iwona, Vandenberghe, Peter, Michaux, Lucienne, 13th Congress of the European-Hematology-Association, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, UCL - SC/CHIM - Département de chimie, UCL - MD/MINT - Département de médecine interne, UCL - (MGD) Laboratoire de biologie clinique, UCL - (MGD) Service d'hématologie, Put, Natalie, Meeus, Peter, Chatelain, Bernard, Stul, M., Boeckx, N., Graux, Carlos, Bries, G., Doyen, Chantal, Dubois, Christine, Marichal, S., Pierre, Patrick, Van Hoof, A., Verschuere, J., Harlet, L., Wlodarska, Iwona, Vandenberghe, Peter, Michaux, Lucienne, and 13th Congress of the European-Hematology-Association

Published
2008

84. Characterization of Nup214-abl1 Positive T-cell Acute Lymphoblastic Leukemia Reveals Genomic Heterogeneity of the Fusion Gene Presentation

Author

UCL - Cliniques universitaires Saint-Luc, UCL - MD/MINT - Département de médecine interne, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, UCL - (MGD) Service d'hématologie, Graux, Carlos, Michaux, Lucienne, Poirel, Hélène, Dastugue, N., Lafage, M., Mugneret, Francine, Struski, S., Gregoire, Michel, Nadal, N., Lippert, E., Stevens-Kroef, M., Vandenberghe, Peter, Bosly, André, Wlodarska, Iwona, Lahortiga, Idoya, De Keersmaecker, Kim, Cools, Jan, Hagemeijer, Anne, UCL - Cliniques universitaires Saint-Luc, UCL - MD/MINT - Département de médecine interne, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, UCL - (MGD) Service d'hématologie, Graux, Carlos, Michaux, Lucienne, Poirel, Hélène, Dastugue, N., Lafage, M., Mugneret, Francine, Struski, S., Gregoire, Michel, Nadal, N., Lippert, E., Stevens-Kroef, M., Vandenberghe, Peter, Bosly, André, Wlodarska, Iwona, Lahortiga, Idoya, De Keersmaecker, Kim, Cools, Jan, and Hagemeijer, Anne

Published
2008

85. BMI1, The polycomb-group gene, is recurrently targeted by genomic rearrangements in progressive B-cell leukemia/lymphoma

Author

Rouhigharabaei, Leila, primary, Ferreiro, Julio Finalet, additional, Put, Natalie, additional, Michaux, Lucienne, additional, Tousseyn, Thomas, additional, Lefebvre, Christine, additional, Gardiner, Anne, additional, De Kelver, Wim, additional, Demuynck, Hilde, additional, Verschuere, Johan, additional, Théate, Ivan, additional, Vicente, Carmen, additional, Vandenberghe, Peter, additional, Cools, Jan, additional, and Wlodarska, Iwona, additional

Published
2013
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86. Single-center analysis of biopsy-confirmed posttransplant lymphoproliferative disorder: incidence, clinicopathological characteristics and prognostic factors

Author

Dierickx, Daan, primary, Tousseyn, Thomas, additional, Sagaert, Xavier, additional, Fieuws, Steffen, additional, Wlodarska, Iwona, additional, Morscio, Julie, additional, Brepoels, Lieselot, additional, Kuypers, Dirk, additional, Vanhaecke, Johan, additional, Nevens, Frederik, additional, Verleden, Geert, additional, Van Damme-Lombaerts, Rita, additional, Renard, Marleen, additional, Pirenne, Jacques, additional, De Wolf-Peeters, Christiane, additional, and Verhoef, Gregor, additional

Published
2013
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87. CCND2 rearrangements are the most frequent genetic events in cyclin D1− mantle cell lymphoma

Author

Salaverria, Itziar, primary, Royo, Cristina, additional, Carvajal-Cuenca, Alejandra, additional, Clot, Guillem, additional, Navarro, Alba, additional, Valera, Alejandra, additional, Song, Joo Y., additional, Woroniecka, Renata, additional, Rymkiewicz, Grzegorz, additional, Klapper, Wolfram, additional, Hartmann, Elena M., additional, Sujobert, Pierre, additional, Wlodarska, Iwona, additional, Ferry, Judith A., additional, Gaulard, Philippe, additional, Ott, German, additional, Rosenwald, Andreas, additional, Lopez-Guillermo, Armando, additional, Quintanilla-Martinez, Leticia, additional, Harris, Nancy L., additional, Jaffe, Elaine S., additional, Siebert, Reiner, additional, Campo, Elias, additional, and Beà, Sílvia, additional

Published
2013
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88. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia

Author

UCL, Lahortiga, Idoya, De Keersmaecker, Kim, Van Vlierberghe, Pieter, Graux, Carlos, Cauwelier, Barbara, Lambert, Frederic, Mentens, Nicole, Beverloo, H. Berna, Pieters, Rob, Speleman, Frank, Odero, Maria D., Bauters, Marijke, Froyen, Guy, Marynen, Peter, Vandenberghe, Peter, Wlodarska, Iwona, Meijerink, Jules P. P., Cools, Jan, UCL, Lahortiga, Idoya, De Keersmaecker, Kim, Van Vlierberghe, Pieter, Graux, Carlos, Cauwelier, Barbara, Lambert, Frederic, Mentens, Nicole, Beverloo, H. Berna, Pieters, Rob, Speleman, Frank, Odero, Maria D., Bauters, Marijke, Froyen, Guy, Marynen, Peter, Vandenberghe, Peter, Wlodarska, Iwona, Meijerink, Jules P. P., and Cools, Jan

Abstract

We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.

Published
2007

89. The T(14;20)(Q32;Q12): A rare cytogenetic change in MM associated with poor outcome

Author

UCL - MD/MINT - Département de médecine interne, Michaux, Lucienne, Lemmens, Heidi, Doyen, Chantal, Lemmens, J., Meeus, Peter, Wlodarska, Iwona, Hagemeijer, Anne, Vandenberghe, Peter, UCL - MD/MINT - Département de médecine interne, Michaux, Lucienne, Lemmens, Heidi, Doyen, Chantal, Lemmens, J., Meeus, Peter, Wlodarska, Iwona, Hagemeijer, Anne, and Vandenberghe, Peter

Published
2007

90. Involvement of the Notch1 and Notch2 genes in B-cell lymphomagen

Author

UCL - Cliniques universitaires Saint-Luc, UCL - MD/MNOP - Département de morphologie normale et pathologique, UCL - MD/MINT - Département de médecine interne, Wlodarska, Iwona, Michaux, Lucienne, De Keersmaecker, Kim, Cools, Jan, De Wolf-Peeters, C., Bosly, André, Delos, Monique, Vanhentenrijk, P., Hagemeijer, Anne, Marynen, Peter, UCL - Cliniques universitaires Saint-Luc, UCL - MD/MNOP - Département de morphologie normale et pathologique, UCL - MD/MINT - Département de médecine interne, Wlodarska, Iwona, Michaux, Lucienne, De Keersmaecker, Kim, Cools, Jan, De Wolf-Peeters, C., Bosly, André, Delos, Monique, Vanhentenrijk, P., Hagemeijer, Anne, and Marynen, Peter

Published
2007

91. Detection of bone marrow involvement in newly diagnosed post-transplant lymphoproliferative disorder: F-fluorodeoxyglucose positron emission tomography/computed tomography versus bone marrow biopsy.

Author

Gheysens, Olivier, Thielemans, Sanne, Morscio, Julie, Boeckx, Nancy, Goffin, Karolien E., Deroose, Christophe M., Sagaert, Xavier, Wlodarska, Iwona, Verhoef, Gregor, Dierickx, Daan, and Tousseyn, Thomas

Subjects
BONE marrow examination, BIOPSY, LYMPHOPROLIFERATIVE disorders, TRANSPLANTATION of organs, tissues, etc., POSITRON emission tomography
Abstract

Detecting bone marrow involvement (BMI) in lymphoma is important as it adversely affects stage. Bone marrow biopsy (BMB) remains the standard to detect BMI but is prone to sampling error. We retrospectively investigated whether18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG-PET/CT) could identify BMI in patients with post-transplant lymphoproliferative disorder (PTLD) with sufficient accuracy in comparison with staging BMB. Twenty-five patients diagnosed with PTLD who underwent18F-FDG-PET/CT and BMB within one month were evaluated. Based on our criteria, six patients (24%) were considered positive for BMI on18F-FDG-PET/CT compared to one by BMB. Although we cannot completely exclude false positive results on18F-FDG-PET/CT, our data indicate a significantly higher sensitivity of18F-FDG-PET/CT compared to BMB (100%vs17%) but similar specificity. These data confirm the high diagnostic performance of18F-FDG-PET/CT for detecting BMI, but prospective studies are needed to determine whether18F-FDG-PET/CT could indeed replace staging BMB in PTLD. [ABSTRACT FROM AUTHOR]

Published
2016
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92. SEC31A-ALK Fusion Gene in Lung Adenocarcinoma.

Author

Ryong Nam Kim, Yoon-La Choi, Mi-Sook Lee, Lira, Maruja E., Mao Mao, Mann, Derrick, Stahl, Joshua, Licon, Abel, So Jung Choi, Van Vrancken, Michael, Joungho Han, Wlodarska, Iwona, and Jhingook Kim

Subjects
ANAPLASTIC lymphoma kinase, CANCER treatment, NON-small-cell lung carcinoma, CARCINOGENESIS, CHIMERIC proteins, ADENOCARCINOMA, FLUORESCENCE in situ hybridization
Abstract

Anaplastic lymphoma kinase (ALK) fusion is a common mechanism underlying pathogenesis of non-small cell lung carcinoma (NSCLC) where these rearrangements represent important diagnostic and therapeutic targets. In this study, we found a new ALK fusion gene, SEC31A-ALK, in lung carcinoma from a 53-year-old Korean man. The conjoined region in the fusion transcript was generated by the fusion of SEC31A exon 21 and ALK exon 20 by genomic rearrangement, which contributed to generation of an intact, in-frame open reading frame. SEC31A-ALK encodes a predicted fusion protein of 1,438 amino acids comprising the WD40 domain of SEC31A at the N-terminus and ALK kinase domain at the C-terminus. Fluorescence in situ hybridization studies suggested that SEC31A-ALK was generated by an unbalanced genomic rearrangement associated with loss of the 3!-end of SEC31A. This is the first report of SEC31A-ALK fusion transcript in clinical NSCLC, which could be a novel diagnostic and therapeutic target for patients with NSCLC. [ABSTRACT FROM AUTHOR]

Published
2016
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93. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia

Author

De Keersmaecker, Kim, primary, Atak, Zeynep Kalender, additional, Li, Ning, additional, Vicente, Carmen, additional, Patchett, Stephanie, additional, Girardi, Tiziana, additional, Gianfelici, Valentina, additional, Geerdens, Ellen, additional, Clappier, Emmanuelle, additional, Porcu, Michaël, additional, Lahortiga, Idoya, additional, Lucà, Rossella, additional, Yan, Jiekun, additional, Hulselmans, Gert, additional, Vranckx, Hilde, additional, Vandepoel, Roel, additional, Sweron, Bram, additional, Jacobs, Kris, additional, Mentens, Nicole, additional, Wlodarska, Iwona, additional, Cauwelier, Barbara, additional, Cloos, Jacqueline, additional, Soulier, Jean, additional, Uyttebroeck, Anne, additional, Bagni, Claudia, additional, Hassan, Bassem A, additional, Vandenberghe, Peter, additional, Johnson, Arlen W, additional, Aerts, Stein, additional, and Cools, Jan, additional

Published
2012
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94. Array-CGH analysis of T-ALL patients and cell lines.

Author

UCL - Autre, Lahortiga, Idoya, Graux, Carlos, Mentens, Nicole, Van Roosbroeck, Katrien, De Keersmaecker, Kim, Lambert, Frederic, Vandenberghe, Peter, Wlodarska, Iwona, Froyen, Guy, Odero, Maria D., Marynen, Peter, Cools, Jan, UCL - Autre, Lahortiga, Idoya, Graux, Carlos, Mentens, Nicole, Van Roosbroeck, Katrien, De Keersmaecker, Kim, Lambert, Frederic, Vandenberghe, Peter, Wlodarska, Iwona, Froyen, Guy, Odero, Maria D., Marynen, Peter, and Cools, Jan

Published
2006

95. Involvement of the NOTCH1 and NOTCH2 genes in B-cell lymphomagenesis.

Author

UCL - Cliniques universitaires Saint-Luc, UCL - MD/MNOP - Département de morphologie normale et pathologique, UCL - MD/MINT - Département de médecine interne, Wlodarska, Iwona, Michaux, Lucienne, De Keersmaecker, Kim, Cools, Jan, De Wolf-Peeters, Chris, Bosly, André, Delos, Monique, Vandenberghe, Peter, Hagemeijer, Anne, Marynen, Peter, 48th Annual Meeting of the American-Society-of-Hematology, UCL - Cliniques universitaires Saint-Luc, UCL - MD/MNOP - Département de morphologie normale et pathologique, UCL - MD/MINT - Département de médecine interne, Wlodarska, Iwona, Michaux, Lucienne, De Keersmaecker, Kim, Cools, Jan, De Wolf-Peeters, Chris, Bosly, André, Delos, Monique, Vandenberghe, Peter, Hagemeijer, Anne, Marynen, Peter, and 48th Annual Meeting of the American-Society-of-Hematology

Published
2006

96. Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma.

Author

[KUL], Sagaert, Xavier, de Paepe, Pascale, Libbrecht, Louis, Vanhentenrijk, Vera, Verhoef, Gregor, Thomas, Jose, Wlodarska, Iwona, De Wolf-Peeters, Christiane, [KUL], Sagaert, Xavier, de Paepe, Pascale, Libbrecht, Louis, Vanhentenrijk, Vera, Verhoef, Gregor, Thomas, Jose, Wlodarska, Iwona, and De Wolf-Peeters, Christiane

Abstract

PURPOSE: Gene expression profiling studies have reported upregulated mRNA expression of forkhead box protein P1 (FOXP1) in response to normal B-cell activation and high expression in a poor prognosis subtype of diffuse large B-cell lymphoma (DLBCL). Recently, it was also found that FOXP1 rearrangements and expression of its protein occur in mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we investigated FOXP1 expression in its relationship to morphology, genetic features, and prognosis in a series of 70 MALT lymphomas. PATIENTS AND METHODS: All samples were morphologically reviewed and stained for FOXP1. Presence of structural and/or numeric aberrations of the FOXP1, BCL10, and MALT1 genes was investigated. For all patients, a complete clinical data set was collected. RESULTS: We detected nuclear expression of FOXP1 in 20 of the 70 MALT lymphomas (nine of them featuring structural or numeric aberrations of the FOXP1 locus). FOXP1 positivity was confined to MALT lymphomas with poor clinical outcome (with impact of FOXP1 expression on relapse rate and disease-free survival). It was also found that MALT lymphomas with strong FOXP1 expression are at risk of transforming into an aggressive DLBCL of nongerminal center phenotype if they feature, in addition, a polymorphic histology and the presence of trisomy 3 and 18. CONCLUSION: The data presented show that FOXP1 expression is an independent prognostic factor in MALT lymphomas. The data also support the hypothesis that a subgroup of nongerminal center DLBCLs (those marked by FOXP1 expression and trisomy 3 and 18) might represent a large-cell variant of MALT lymphomas.

Published
2006

97. FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations

Author

UCL - MD/MINT - Département de médecine interne, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service d'hématologie, Wlodarska, Iwona, Veyt, E, De Paepe, P, Vandenberghe, Peter, Nooijen, P, Théate, Ivan, Michaux, Lucienne, Sagaert, X, Marynen, Peter, Hagemeijer, Anne, De Wolf- Peeters, C, UCL - MD/MINT - Département de médecine interne, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service d'hématologie, Wlodarska, Iwona, Veyt, E, De Paepe, P, Vandenberghe, Peter, Nooijen, P, Théate, Ivan, Michaux, Lucienne, Sagaert, X, Marynen, Peter, Hagemeijer, Anne, and De Wolf- Peeters, C

Abstract

The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization ( FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( x 1), gastric MALT lymphoma ( x 1) and B-cell non-Hodgkin's lymphoma, not otherwise specified ( x 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene.

Published
2005

98. Translocation t(1;6)(p35.3;p25.2): a new recurrent aberration in 'unmutated' B-CLL

Author

UCL - MD/MINT - Département de médecine interne, UCL - (SLuc) Service d'hématologie, Michaux, Lucienne, Wlodarska, Iwona, Rack, K., Stul, M., Criel, A., Maerevoet, M., Marichal, S., Demuynck, H., Mineur, P., Samani, KK, Van Hoof, A., Ferrant, Augustin, Marynen, Peter, Hagemeijer, Anne, UCL - MD/MINT - Département de médecine interne, UCL - (SLuc) Service d'hématologie, Michaux, Lucienne, Wlodarska, Iwona, Rack, K., Stul, M., Criel, A., Maerevoet, M., Marichal, S., Demuynck, H., Mineur, P., Samani, KK, Van Hoof, A., Ferrant, Augustin, Marynen, Peter, and Hagemeijer, Anne

Abstract

Although reciprocal chromosomal translocations are not typical for B-cell chronic lymphocytic leukemia (B-CLL), we identified the novel t(1;6)(p35.3;p25.2) in eight patients with this disorder. Interestingly, all cases showed lack of somatically mutated IgV(H). Clinical, morphological, immunologic, and genetic features of these patients are described. Briefly, the age ranged from 33 to 81 years (median: 62.5 years) and the sex ratio was 6M:2F. Most of the patients (6/8) presented with advanced clinical stage. Therapy was required in seven cases. After a median follow-up of 28 months, five patients are alive and three died from disease evolution. Three cases developed transformation into diffuse large B-cell lymphoma. Translocation t(1;6) was found as the primary karyotypic abnormality in three patients. Additional chromosomal aberrations included changes frequently found in unmutated B-CLL, that is, del(11)(q), trisomy 12 and 17p aberrations. Fluorescence in situ hybridization analysis performed in seven cases allowed us to map the t( 1; 6) breakpoints to the 1p35.3 and 6p25.2 chromosomal bands, respectively. The latter breakpoint was located in the genomic region coding for MUM1/IRF4, one of the key regulators of lymphocyte development and proliferation, suggesting involvement of this gene in the t(1;6). Molecular characterization of the t(1;6)(p35.3; p25.2), exclusively found in unmutated subtype of B-CLL, is in progress.

Published
2005

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