PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas

Giosuè Scognamiglio, Elena Valentino, Michela Vitiello, Antonio Luciano, Giuseppe Palma, Claudio Arra, Elvira La Mantia, Luigi Panico, Valentina Tenneriello, Antonello Pinto, Ferdinando Frigeri, Gaetana Capobianco, Gerardo Botti, Laura Cerchia, Annarosaria De Chiara, Monica Fedele

Research output: Contribution to journalArticle

Abstract

Non-Hodgkin lymphomas (NHLs) include a heterogeneous group of diseases, which differ in both cellular origin and clinical behavior. Among the aggressive malignancies of this group, the diffuse large B-cell lymphomas (DLBCLs) are the most frequently observed. They are themselves clinically and molecularly heterogeneous and have been further sub-divided in three sub-types according to different cell of origin, mechanisms of oncogenesis and clinical outcome. Among them, the germinal center B-cell-like (GCB) derives from the germinal center and expresses the BCL6 oncogene. We have previously shown that Patz1-knockout mice develop B-cell neoplasias, suggesting a tumor suppressor role for PATZ1 in human NHLs. Here, by immunohistochemical analysis of a tissue-microarray including 170 NHLs, we found that PATZ1 nuclear expression is downregulated in follicular lymphomas and DLBCLs. Moreover, consistent with our previous results showing a PATZ1-dependent regulation of BCL6 and BAX transcription, we show that low PATZ1 nuclear expression significantly correlates with high BCL6 expression, mainly in DLBCLs, and with low BAX expression, also considering separately follicular lymphomas and DLBCLs. Finally, by analyzing overall and progression-free survival in DLBCL patients that underwent rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, low levels of PATZ1 were significantly associated to a worst outcome and demonstrated an independent prognostic factor in multivariate analysis, including known prognostic factors of DLBCL, IPI score and cell of origin (GCB/non-GCB). Therefore, we propose PATZ1 as a new prognostic marker of DLBCLs, which may act as a tumor suppressor by enhancing apoptosis through inhibiting and enhancing transcription of BCL6 and BAX, respectively.

Original languageEnglish
Pages (from-to)59158-59172
Number of pages15
JournalOncotarget
Volume7
Issue number37
DOIs
Publication statusPublished - 2016

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Survival
Germinal Center
B-Lymphocytes
Non-Hodgkin's Lymphoma
Follicular Lymphoma
Neoplasms
Tissue Array Analysis
Vincristine
Prednisone
Oncogenes
Knockout Mice
Doxorubicin
Cyclophosphamide
Disease-Free Survival
Carcinogenesis
Down-Regulation
Multivariate Analysis
Apoptosis
Drug Therapy

Keywords

  • DLBCL
  • Non-Hodgkin lymphomas
  • PATZ1
  • Prognostic marker
  • Tissue-microarray

ASJC Scopus subject areas

  • Oncology

Cite this

PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas. / Scognamiglio, Giosuè; Valentino, Elena; Vitiello, Michela; Luciano, Antonio; Palma, Giuseppe; Arra, Claudio; La Mantia, Elvira; Panico, Luigi; Tenneriello, Valentina; Pinto, Antonello; Frigeri, Ferdinando; Capobianco, Gaetana; Botti, Gerardo; Cerchia, Laura; De Chiara, Annarosaria; Fedele, Monica.

In: Oncotarget, Vol. 7, No. 37, 2016, p. 59158-59172.

Research output: Contribution to journalArticle

Scognamiglio, G, Valentino, E, Vitiello, M, Luciano, A, Palma, G, Arra, C, La Mantia, E, Panico, L, Tenneriello, V, Pinto, A, Frigeri, F, Capobianco, G, Botti, G, Cerchia, L, De Chiara, A & Fedele, M 2016, 'PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas', Oncotarget, vol. 7, no. 37, pp. 59158-59172. https://doi.org/10.18632/oncotarget.10993
Scognamiglio, Giosuè ; Valentino, Elena ; Vitiello, Michela ; Luciano, Antonio ; Palma, Giuseppe ; Arra, Claudio ; La Mantia, Elvira ; Panico, Luigi ; Tenneriello, Valentina ; Pinto, Antonello ; Frigeri, Ferdinando ; Capobianco, Gaetana ; Botti, Gerardo ; Cerchia, Laura ; De Chiara, Annarosaria ; Fedele, Monica. / PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas. In: Oncotarget. 2016 ; Vol. 7, No. 37. pp. 59158-59172.
@article{9450083336f24f9dace982656ae6f6c7,
title = "PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas",
abstract = "Non-Hodgkin lymphomas (NHLs) include a heterogeneous group of diseases, which differ in both cellular origin and clinical behavior. Among the aggressive malignancies of this group, the diffuse large B-cell lymphomas (DLBCLs) are the most frequently observed. They are themselves clinically and molecularly heterogeneous and have been further sub-divided in three sub-types according to different cell of origin, mechanisms of oncogenesis and clinical outcome. Among them, the germinal center B-cell-like (GCB) derives from the germinal center and expresses the BCL6 oncogene. We have previously shown that Patz1-knockout mice develop B-cell neoplasias, suggesting a tumor suppressor role for PATZ1 in human NHLs. Here, by immunohistochemical analysis of a tissue-microarray including 170 NHLs, we found that PATZ1 nuclear expression is downregulated in follicular lymphomas and DLBCLs. Moreover, consistent with our previous results showing a PATZ1-dependent regulation of BCL6 and BAX transcription, we show that low PATZ1 nuclear expression significantly correlates with high BCL6 expression, mainly in DLBCLs, and with low BAX expression, also considering separately follicular lymphomas and DLBCLs. Finally, by analyzing overall and progression-free survival in DLBCL patients that underwent rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, low levels of PATZ1 were significantly associated to a worst outcome and demonstrated an independent prognostic factor in multivariate analysis, including known prognostic factors of DLBCL, IPI score and cell of origin (GCB/non-GCB). Therefore, we propose PATZ1 as a new prognostic marker of DLBCLs, which may act as a tumor suppressor by enhancing apoptosis through inhibiting and enhancing transcription of BCL6 and BAX, respectively.",
keywords = "DLBCL, Non-Hodgkin lymphomas, PATZ1, Prognostic marker, Tissue-microarray",
author = "Giosu{\`e} Scognamiglio and Elena Valentino and Michela Vitiello and Antonio Luciano and Giuseppe Palma and Claudio Arra and {La Mantia}, Elvira and Luigi Panico and Valentina Tenneriello and Antonello Pinto and Ferdinando Frigeri and Gaetana Capobianco and Gerardo Botti and Laura Cerchia and {De Chiara}, Annarosaria and Monica Fedele",
year = "2016",
doi = "10.18632/oncotarget.10993",
language = "English",
volume = "7",
pages = "59158--59172",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "37",

}

TY - JOUR

T1 - PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas

AU - Scognamiglio, Giosuè

AU - Valentino, Elena

AU - Vitiello, Michela

AU - Luciano, Antonio

AU - Palma, Giuseppe

AU - Arra, Claudio

AU - La Mantia, Elvira

AU - Panico, Luigi

AU - Tenneriello, Valentina

AU - Pinto, Antonello

AU - Frigeri, Ferdinando

AU - Capobianco, Gaetana

AU - Botti, Gerardo

AU - Cerchia, Laura

AU - De Chiara, Annarosaria

AU - Fedele, Monica

PY - 2016

Y1 - 2016

N2 - Non-Hodgkin lymphomas (NHLs) include a heterogeneous group of diseases, which differ in both cellular origin and clinical behavior. Among the aggressive malignancies of this group, the diffuse large B-cell lymphomas (DLBCLs) are the most frequently observed. They are themselves clinically and molecularly heterogeneous and have been further sub-divided in three sub-types according to different cell of origin, mechanisms of oncogenesis and clinical outcome. Among them, the germinal center B-cell-like (GCB) derives from the germinal center and expresses the BCL6 oncogene. We have previously shown that Patz1-knockout mice develop B-cell neoplasias, suggesting a tumor suppressor role for PATZ1 in human NHLs. Here, by immunohistochemical analysis of a tissue-microarray including 170 NHLs, we found that PATZ1 nuclear expression is downregulated in follicular lymphomas and DLBCLs. Moreover, consistent with our previous results showing a PATZ1-dependent regulation of BCL6 and BAX transcription, we show that low PATZ1 nuclear expression significantly correlates with high BCL6 expression, mainly in DLBCLs, and with low BAX expression, also considering separately follicular lymphomas and DLBCLs. Finally, by analyzing overall and progression-free survival in DLBCL patients that underwent rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, low levels of PATZ1 were significantly associated to a worst outcome and demonstrated an independent prognostic factor in multivariate analysis, including known prognostic factors of DLBCL, IPI score and cell of origin (GCB/non-GCB). Therefore, we propose PATZ1 as a new prognostic marker of DLBCLs, which may act as a tumor suppressor by enhancing apoptosis through inhibiting and enhancing transcription of BCL6 and BAX, respectively.

AB - Non-Hodgkin lymphomas (NHLs) include a heterogeneous group of diseases, which differ in both cellular origin and clinical behavior. Among the aggressive malignancies of this group, the diffuse large B-cell lymphomas (DLBCLs) are the most frequently observed. They are themselves clinically and molecularly heterogeneous and have been further sub-divided in three sub-types according to different cell of origin, mechanisms of oncogenesis and clinical outcome. Among them, the germinal center B-cell-like (GCB) derives from the germinal center and expresses the BCL6 oncogene. We have previously shown that Patz1-knockout mice develop B-cell neoplasias, suggesting a tumor suppressor role for PATZ1 in human NHLs. Here, by immunohistochemical analysis of a tissue-microarray including 170 NHLs, we found that PATZ1 nuclear expression is downregulated in follicular lymphomas and DLBCLs. Moreover, consistent with our previous results showing a PATZ1-dependent regulation of BCL6 and BAX transcription, we show that low PATZ1 nuclear expression significantly correlates with high BCL6 expression, mainly in DLBCLs, and with low BAX expression, also considering separately follicular lymphomas and DLBCLs. Finally, by analyzing overall and progression-free survival in DLBCL patients that underwent rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, low levels of PATZ1 were significantly associated to a worst outcome and demonstrated an independent prognostic factor in multivariate analysis, including known prognostic factors of DLBCL, IPI score and cell of origin (GCB/non-GCB). Therefore, we propose PATZ1 as a new prognostic marker of DLBCLs, which may act as a tumor suppressor by enhancing apoptosis through inhibiting and enhancing transcription of BCL6 and BAX, respectively.

KW - DLBCL

KW - Non-Hodgkin lymphomas

KW - PATZ1

KW - Prognostic marker

KW - Tissue-microarray

UR - http://www.scopus.com/inward/record.url?scp=84991380581&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991380581&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.10993

DO - 10.18632/oncotarget.10993

M3 - Article

AN - SCOPUS:84991380581

VL - 7

SP - 59158

EP - 59172

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 37

ER -