Loss of a novel tumor suppressor gene locus at chromosome 8p is associated with leukemic mantle cell lymphoma

Martínez-Climent, José A.; Vizcarra, E; Sanchez, Dolors; Blesa, David; Marugán, Isabel; Benet, Isabel; Solé, Françesc; Rubio-Moscardó, Fanny; Terol, María José; Climent, Joan; Sarsotti, Elena; Tormo, Mar; Andreu, Enrique J.; Salido, Marta; Ruiz, María Ángeles; Prósper, Felipe; Siebert, Reiner; Dyer, Martin J. S.; Garcı́a-Conde, J

doi:10.1182/blood.v98.12.3479

Cited by 87 publications

(78 citation statements)

References 17 publications

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“…4d). Nevertheless, specific genomic changes associated with leukemic dissemination and shorter survival times have been observed previously [63,64]. The TF IRF-4 known to separate DLBCL-nonGC from DLBCL-GC [57] and to be expressed in a variety of lymphomas of mature B cells research article American Journal of Hematology(CLL, MM, DLBCL-nonGC) [57,65,66] here show an high mRNA expression in MCL.…”

Section: Discussionmentioning

confidence: 54%

Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

et al. 2010

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Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance to normal B-cells; assessed by immunohistochemistry or flow cytometry, by using a handful of phenotypic markers. In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), providing a new powerful means for the classification, prediction of survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified transcription factors influence both the global and specific gene expression of the BCLs and have possible implications for diagnosis and treatment. Am. J. Hematol. 85:418-425, 2010. V

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Section: Discussionmentioning

confidence: 54%

Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

et al. 2010

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“…Although numerous genomic changes of MCL were identified by array CGH, many of them were the same as those previously listed in reports of studies using chromosomal CGH (also known as conventional CGH). Several authors (Monni et al, 1998;Bea`et al, 1999;Bentz et al, 2000;Martinez-Climent et al, 2001;Allen et al, 2002) reported recurrent regions of gain as 3q (40-70%), 6p (20%), 7p (27%), 8q (20-30%), 10p (20%), 12q (20-30%), 18q21 (20%) and recurrent regions of loss as 1p (24-33%), 6q (27-37%), 8p (20-30%), 9p (16-30%), 11q (22-30%) and 13q (40-60%). However, the incidence of genomic aberrations identified by array CGH was generally higher than that reported in chromosomal CGH studies.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the presence of this common molecular marker, experiments with transgenic mice overexpressing CCND1 proved that this protein alone cannot induce lymphomas (Hinds et al, 1994;Lovec et al, 1994), so that genomic aberrations other than the 11q13 translocation must be involved in the development and progression of MCL. To identify such additional aberrations, several studies using comparative genomic hybridization (CGH) and chromosome banding analyses have been conducted (Monni et al, 1998;Bea`et al, 1999;Cuneo et al, 1999;Bentz et al, 2000;Bigoni et al, 2001;Martinez-Climent et al, 2001;Allen et al, 2002). These studies showed that genomic imbalances, such as gain/amplification of 3q, 6p, 7p, 8q, 10p, 12q and 18q, and loss/deletion of 1p, 6q, 8p, 9p, 11q and 13q, frequently occur in MCL.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide array-based CGH for mantle cell lymphoma: identification of homozygous deletions of the proapoptotic gene BIM

et al. 2004

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Mantle cell lymphoma (MCL) is characterized by 11q13 chromosomal translocation and CCND1 overexpression, but additional genomic changes are also important for lymphomagenesis. To identify the genomic aberrations of MCL at higher resolutions, we analysed 29 patient samples and seven cell lines using array-based comparative genomic hybridization (array CGH) consisting of 2348 artificial chromosome clones, which cover the whole genome at a 1.3 mega base resolution. The incidence of identified genomic aberrations was generally higher than that determined with chromosomal CGH. The most frequent imbalances detected by array CGH were gains of chromosomes 3q26 (48%), 7p21 (34%), 6p25 (24%), 8q24 (24%), 10p12 (21%) and 17q23 (17%), and losses of chromosomes 2p11 (83%), 11q22 (59%), 13q21 (55%), 1p21-p22 (52%), 13q34 (52%), 9q22 (45%), 17p13 (45%), 9p21 (41%), 9p24 (41%), 6q23-q24 (38%), 1p36 (31%), 8p23 (34%), 10p14 (31%), 19p13 (28%), 5q21 (21%), 22q12 (21%), 1q42 (17%) and 2q13 (17%). Our analyses also detected several novel recurrent regions of loss located at 1p36, 1q42.2-q43, 2p11.2, 2q13, 17p13.3 and 19p13.2-p13.3, as well as recurrent regions of homozygous loss such as 2p11 (Igj), 2q13 and 9p21.3-p24.1 (INK4a/ARF). Of the latter, we investigated the 2q13 loss, which led to identification of homozygous deletions of the proapoptotic gene BIM. The highresolution array CGH technology allowed for the precise identification of genomic aberrations and identification of BIM as a novel candidate tumor suppressor gene in MCL.

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“…1). We used the CD20 ϩ Z138 cell line, a mature B cell acute lymphoblastic leukemia line, recognized as a model for mantle cell lymphoma (41,49,50), for most experiments. However, to test for generality, we also examined Raji and ARH77 cells as well as primary malignant B cells from CLL patients (13,34,39).…”

Section: Experimental Paradigmmentioning

confidence: 99%

The Shaving Reaction: Rituximab/CD20 Complexes Are Removed from Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Cells by THP-1 Monocytes

Beum

Kennedy

Williams

et al. 2006

The Journal of Immunology

209

226

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Clinical investigations have revealed that infusion of immunotherapeutic mAbs directed to normal or tumor cells can lead to loss of targeted epitopes, a phenomenon called antigenic modulation. Recently, we reported that rituximab treatment of chronic lymphocytic leukemia patients induced substantial loss of CD20 on B cells found in the circulation after rituximab infusion, when rituximab plasma concentrations were high. Such antigenic modulation can severely compromise therapeutic efficacy, and we postulated that B cells had been stripped (shaved) of the rituximab/CD20 complex by monocytes or macrophages in a reaction mediated by FcγR. We developed an in vitro model to replicate this in vivo shaving process, based on reacting rituximab-opsonized CD20+ cells with acceptor THP-1 monocytes. After 45 min at 37°C, rituximab and CD20 are removed from opsonized cells, and both are demonstrable on acceptor THP-1 cells. The reaction occurs equally well in the presence and absence of normal human serum, and monocytes isolated from peripheral blood also promote shaving of CD20 from rituximab-opsonized cells. Tests with inhibitors and use of F(ab′)2 of rituximab indicate transfer of rituximab/CD20 complexes to THP-1 cells is mediated by FcγR. Antigenic modulation described in previous reports may have been mediated by such shaving, and our findings may have profound implications for the use of mAbs in the immunotherapy of cancer.

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Loss of a novel tumor suppressor gene locus at chromosome 8p is associated with leukemic mantle cell lymphoma

Cited by 87 publications

References 17 publications

Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

Genome-wide array-based CGH for mantle cell lymphoma: identification of homozygous deletions of the proapoptotic gene BIM

The Shaving Reaction: Rituximab/CD20 Complexes Are Removed from Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Cells by THP-1 Monocytes

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