PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma.

Michela Boi, Andrea Rinaldi, Ivo Kwee, Paola Bonetti, Maria Todaro, Fabrizio Tabbò, Roberto Piva, Paola M V Rancoita, A. Matolcsy, Botond Timar, Thomas Tousseyn, Socorro Maria Rodríguez-Pinilla, Miguel A. Piris, Sílvia Beà, Elias Campo, Govind Bhagat, Steven H. Swerdlow, Andreas Rosenwald, Maurilio Ponzoni, Ken H. Young & 6 others Pier Paolo Piccaluga, Reinhard Dummer, Stefano Pileri, Emanuele Zucca, Giorgio Inghirami, Francesco Bertoni

Research output: Contribution to journalArticle

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Abstract

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that can present as a systemic or primary cutaneous disease. Systemic ALCL represents 2% to 5% of adult lymphoma but up to 30% of all pediatric cases. Two subtypes of systemic ALCL are currently recognized on the basis of the presence of a translocation involving the anaplastic lymphoma kinase ALK gene. Despite considerable progress, several questions remain open regarding the pathogenesis of both ALCL subtypes. To investigate the molecular pathogenesis and to assess the relationship between the ALK(+) and ALK(-) ALCL subtypes, we performed a genome-wide DNA profiling using high-density, single nucleotide polymorphism arrays on a series of 64 cases and 7 cell lines. The commonest lesions were losses at 17p13 and at 6q21, encompassing the TP53 and PRDM1 genes, respectively. The latter gene, coding for BLIMP1, was inactivated by multiple mechanisms, more frequently, but not exclusively, in ALK(-)ALCL. In vitro and in vivo experiments showed that that PRDM1 is a tumor suppressor gene in ALCL models, likely acting as an antiapoptotic agent. Losses of TP53 and/or PRDM1 were present in 52% of ALK(-)ALCL, and in 29% of all ALCL cases with a clinical implication.

Original languageEnglish
Pages (from-to)2683-2693
Number of pages11
JournalBlood
Volume122
Issue number15
Publication statusPublished - Oct 10 2013

Fingerprint

Anaplastic Large-Cell Lymphoma
T-cells
T-Cell Lymphoma
Genes
Pediatrics
Polymorphism
Tumors
Nucleotides
Cells
DNA Fingerprinting
p53 Genes
DNA
Tumor Suppressor Genes
Skin Diseases
Single Nucleotide Polymorphism
Lymphoma
Genome
Experiments
Cell Line

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

Cite this

Boi, M., Rinaldi, A., Kwee, I., Bonetti, P., Todaro, M., Tabbò, F., ... Bertoni, F. (2013). PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma. Blood, 122(15), 2683-2693.

PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma. / Boi, Michela; Rinaldi, Andrea; Kwee, Ivo; Bonetti, Paola; Todaro, Maria; Tabbò, Fabrizio; Piva, Roberto; Rancoita, Paola M V; Matolcsy, A.; Timar, Botond; Tousseyn, Thomas; Rodríguez-Pinilla, Socorro Maria; Piris, Miguel A.; Beà, Sílvia; Campo, Elias; Bhagat, Govind; Swerdlow, Steven H.; Rosenwald, Andreas; Ponzoni, Maurilio; Young, Ken H.; Piccaluga, Pier Paolo; Dummer, Reinhard; Pileri, Stefano; Zucca, Emanuele; Inghirami, Giorgio; Bertoni, Francesco.

In: Blood, Vol. 122, No. 15, 10.10.2013, p. 2683-2693.

Research output: Contribution to journalArticle

Boi, M, Rinaldi, A, Kwee, I, Bonetti, P, Todaro, M, Tabbò, F, Piva, R, Rancoita, PMV, Matolcsy, A, Timar, B, Tousseyn, T, Rodríguez-Pinilla, SM, Piris, MA, Beà, S, Campo, E, Bhagat, G, Swerdlow, SH, Rosenwald, A, Ponzoni, M, Young, KH, Piccaluga, PP, Dummer, R, Pileri, S, Zucca, E, Inghirami, G & Bertoni, F 2013, 'PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma.', Blood, vol. 122, no. 15, pp. 2683-2693.
Boi M, Rinaldi A, Kwee I, Bonetti P, Todaro M, Tabbò F et al. PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma. Blood. 2013 Oct 10;122(15):2683-2693.
Boi, Michela ; Rinaldi, Andrea ; Kwee, Ivo ; Bonetti, Paola ; Todaro, Maria ; Tabbò, Fabrizio ; Piva, Roberto ; Rancoita, Paola M V ; Matolcsy, A. ; Timar, Botond ; Tousseyn, Thomas ; Rodríguez-Pinilla, Socorro Maria ; Piris, Miguel A. ; Beà, Sílvia ; Campo, Elias ; Bhagat, Govind ; Swerdlow, Steven H. ; Rosenwald, Andreas ; Ponzoni, Maurilio ; Young, Ken H. ; Piccaluga, Pier Paolo ; Dummer, Reinhard ; Pileri, Stefano ; Zucca, Emanuele ; Inghirami, Giorgio ; Bertoni, Francesco. / PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma. In: Blood. 2013 ; Vol. 122, No. 15. pp. 2683-2693.
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abstract = "Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that can present as a systemic or primary cutaneous disease. Systemic ALCL represents 2{\%} to 5{\%} of adult lymphoma but up to 30{\%} of all pediatric cases. Two subtypes of systemic ALCL are currently recognized on the basis of the presence of a translocation involving the anaplastic lymphoma kinase ALK gene. Despite considerable progress, several questions remain open regarding the pathogenesis of both ALCL subtypes. To investigate the molecular pathogenesis and to assess the relationship between the ALK(+) and ALK(-) ALCL subtypes, we performed a genome-wide DNA profiling using high-density, single nucleotide polymorphism arrays on a series of 64 cases and 7 cell lines. The commonest lesions were losses at 17p13 and at 6q21, encompassing the TP53 and PRDM1 genes, respectively. The latter gene, coding for BLIMP1, was inactivated by multiple mechanisms, more frequently, but not exclusively, in ALK(-)ALCL. In vitro and in vivo experiments showed that that PRDM1 is a tumor suppressor gene in ALCL models, likely acting as an antiapoptotic agent. Losses of TP53 and/or PRDM1 were present in 52{\%} of ALK(-)ALCL, and in 29{\%} of all ALCL cases with a clinical implication.",
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AU - Boi, Michela

AU - Rinaldi, Andrea

AU - Kwee, Ivo

AU - Bonetti, Paola

AU - Todaro, Maria

AU - Tabbò, Fabrizio

AU - Piva, Roberto

AU - Rancoita, Paola M V

AU - Matolcsy, A.

AU - Timar, Botond

AU - Tousseyn, Thomas

AU - Rodríguez-Pinilla, Socorro Maria

AU - Piris, Miguel A.

AU - Beà, Sílvia

AU - Campo, Elias

AU - Bhagat, Govind

AU - Swerdlow, Steven H.

AU - Rosenwald, Andreas

AU - Ponzoni, Maurilio

AU - Young, Ken H.

AU - Piccaluga, Pier Paolo

AU - Dummer, Reinhard

AU - Pileri, Stefano

AU - Zucca, Emanuele

AU - Inghirami, Giorgio

AU - Bertoni, Francesco

PY - 2013/10/10

Y1 - 2013/10/10

N2 - Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that can present as a systemic or primary cutaneous disease. Systemic ALCL represents 2% to 5% of adult lymphoma but up to 30% of all pediatric cases. Two subtypes of systemic ALCL are currently recognized on the basis of the presence of a translocation involving the anaplastic lymphoma kinase ALK gene. Despite considerable progress, several questions remain open regarding the pathogenesis of both ALCL subtypes. To investigate the molecular pathogenesis and to assess the relationship between the ALK(+) and ALK(-) ALCL subtypes, we performed a genome-wide DNA profiling using high-density, single nucleotide polymorphism arrays on a series of 64 cases and 7 cell lines. The commonest lesions were losses at 17p13 and at 6q21, encompassing the TP53 and PRDM1 genes, respectively. The latter gene, coding for BLIMP1, was inactivated by multiple mechanisms, more frequently, but not exclusively, in ALK(-)ALCL. In vitro and in vivo experiments showed that that PRDM1 is a tumor suppressor gene in ALCL models, likely acting as an antiapoptotic agent. Losses of TP53 and/or PRDM1 were present in 52% of ALK(-)ALCL, and in 29% of all ALCL cases with a clinical implication.

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