Lymphoid Neoplasms

  • Navarro Group
Campus ICO-Germans Trias i Pujol

Laboratory of Hematology
Germans Trias i Pujol Hospital
Carretera de Canyet s/n
08916 Badalona
Barcelona
Spain

 

Directions

Summary

The Lymphoid Neoplasms Group is led by Tomàs Navarro,and Juan Manuel Sancho, both attending physicians in Department of Haematology-Laboratory at the Catalan Institute of Oncology (ICO)- Germans Trias i Pujol Hospital. Dr Navarro is responsible for the cytomorphological diagnosis of lymphomas. Amongst its other activities the group works on projects administered by the Josep Carreras Leukaemia Research Institute (IJC). Dr Maria Joao Baptista is a full-time researcher for the IJC dedicated to these projects.

Research focuses on the study of clinical aspects and biological mechanisms of aggressive lymphomas, especially in HIV-infected patients. The research lines are: the study of the influence of viruses on the genetic and epigenetic mechanisms of lymphomagenesis and the implication of glycoproteins in the dissemination of lymphomas. Studies include the role of miRNAs in the lymphomagenesis of HIV-related non-Hodgkin’s lymphomas, and the correlation of genetic and epigenetic profiles with the clinical-biological features and the prognosis of aggressive lymphomas. Future projects will focus on the mechanisms of lymphoma dissemination, especially to central nervous system.

Research

We focus our scientific interests mainly on aggressive B-cell lymphomas and especially HIV-related ones.

Aggressive B-cell lymphomas mainly include diffuse large B cell lymphoma (DLBCL) and Burkitt's lymphoma (BL) but also other lymphoma entities. Aggressive B-cell lymphomas present heterogeneous biological characteristics and clinical behaviour. Hence, there is a need to find new biological markers that could identify patients with poor prognosis to whom to administer treatment or therapeutic targets to. The incidence of aggressive B-cell non-Hodgkin's lymphoma (NHL) is increased among HIV-infected individuals. Characteristically, the NHL of HIV-infected individuals are aggressive B-cell lymphomas with DLBCL and BL being the most commons.

Prognostic impact of gene rearrangements and of protein expression in HIV related lymphomas

Rearrangements of the genes BCL2, BCL6 and MYC have been recently reported to be bad prognostic markers. The prognosis value of these genetic and molecular abnormalities has been little studied in HIV-related lymphomas. Our group together with the pathologists Dr. JL Mate and Dr. G Tapia, is running a project with the aim of unveiling the influence of the HIV infection in the frequency of BCL2, BCL6 and MYC rearrangements and to compare the expression level pattern of the proteins BCL2 and MYC between HIV-related lymphomas and HIV-negative lymphomas. The expression of these proteins on lymphomas has been demonstrated to have a bad prognostic impact among HIV-negative patients with DLBCL. Hence we will also establish the prognostic value of BCL2, BCL6 and MYC rearrangements, as well as proteins BCL2 and MYC, in the patients with HIV-related lymphoma. We plan to correlate the data of BCL2, BCL6 and MYC rearrangements and of BCL2 and MYC expression patterns with the clinical-biological lymphoma features and to seek for differences between the HIV-negative and the HIV-related lymphomas.

Expression profile and prognostic value of miRNAs in aggressive B-cell non Hodgkin lymphomas associated with HIV infection

The miRNAs are a group of non-coding RNAs capable of regulating the expression of mRNAs at post-transcriptional level. Recently, many miRNAs have been identified as being involved in cancer, acting either as oncogenes or tumour suppressors. Recent studies have identified some miRNAs with a different expression in DLBCL cells with respect to normal lymphoid tissue.

We aim to study the miRNA expression profile in the HIV infected population with aggressive NHL and to determine miRNAs with potential prognostic value. Also, we are going to compare the miRNA expression profiles of the HIV infected and non-infected population. The specific aims are to determine the frequency and the prognostic value of the expression levels of the miRNAs related to the MYC gene as well as the miRNAs with reported prognostic value in HIV-negative DLBCL in HIV-related lymphom. We are going to compare the expression level pattern of these miRNAs between HIV-related lymphomas and HIV-negative lymphomas. Furthermore we will correlate the data of the miRNA expression patterns with the clinical-biological lymphoma features to look for differences between the HIV-negative and the HIV-related lymphomas.

This project involves multiple centers. At the IJC it is being carried out by Maria Joao Baptista and we have the collaboration of several hospitals throughout Spain.

PLEASE NOTE THAT THE RESEARCH PUBLICATIONS SHOWN HERE ARE FOR MJ BAPTISTA, NOT THE GROUP

Collaborations

The Lymphoid Neoplasms Group works with many other groups on joint projects

Department of Pathology, Germans Trias i Pujol Hospital
Dr José luis Mate Sanz
Dr Gustavo Tapia Melendo
Ana Maria Muñoz Marmol
Carolina Sanz

Department of Laboratoy of Hematology, ICO-Badalona
Prof Dr Evarist Feliu
Dr Fuensanta Milla
Neus Ruiz Xivilé

Department of Clinical Hematology, ICO-Badalona
Dr Jose Maria Ribera
Dr Miriam Moreno

HIV-Unit, Germans Trias i Pujol Hospital
Dr Guillem Sirera
Dr Cristina Tural

IRSI-Caixa, Germans Trias i Pujol Hospital
Xavier Martinez Picado

Dr Silvia Montoto, Centre for Haemato-Oncology, Barts Cancer Institute-Queen Mary, University of London

Prof Riccardo Dolcetti National Cancer Insitute (CRO), Aviano. Italy

Prof Robert Sackstein. Brigham and Women’s Hospital Harvard Medical School. Boston, Massachusetts

People

Selected publications

Sorigue M, Garcia O, Baptista MJ, Sancho JM, Tapia G, Mate JL, Feliu E, Navarro JT, Ribera JM

Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy.

Med Clin (Barc) 27 Dec 2016, . Epub 27 Dec 2016
The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab.
More information
Baptista MJ, Hernandez-Rodriguez A, Martinez-Caceres E, Morgades M, Martinez-Picado J, Sirera G, Sancho JM, Feliu E, Ribera JM, Navarro JT

Epstein-Barr viral loads and serum free light chains levels are potential follow-up markers of HIV-related lymphomas.

Leuk. Lymphoma 28 Apr 2016, 1-3. Epub 28 Apr 2016More information
Baptista MJ, Garcia O, Morgades M, Gonzalez-Barca E, Miralles P, Lopez-Guillermo A, Abella E, Moreno M, Sancho JM, Feliu E, Ribera JM, Navarro JT

HIV-infection impact on clinical-biological features and outcome of diffuse large B-cell lymphoma treated with R-CHOP in the combination antiretroviral therapy era.

AIDS 24 Apr 2015, 29 (7) 811-8. Epub 27 Feb 2015
Since the introduction of combination antiretroviral therapy (cART) patients with HIV-related diffuse large B-cell lymphoma (DLBCL) show better control of immunosuppression, which may have an impact on the characteristics and prognosis of the disease. We aimed to compare the clinical presentation and prognosis of patients with HIV-related and HIV-unrelated DLBCL treated with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) in the cART era.
More information
Tapia G, Baptista MJ, Muñoz-Marmol AM, Gaafar A, Puente-Pomposo M, Garcia O, Marginet-Flinch R, Sanz C, Navarro JT, Sancho JM, Ribera JM, Ariza A, Mate JL

MYC protein expression is associated with poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system.

APMIS Jul 2015, 123 (7) 596-603. Epub 22 May 2015
MYC and BCL2 gene translocations and protein expression have recently demonstrated to be of prognostic significance in systemic diffuse large B-cell lymphoma (DLBCL). However, their role in primary central nervous system DLBCL (CNS-DLBCL) prognosis has been scarcely analyzed. We studied the immunophenotype, the status of the MYC, BCL2, and BCL6 genes and the clinical features of a series of 42 CNS-DLBCL and evaluated their prognostic significance. We found high MYC protein expression in 43% of cases, and this was associated with lower overall survival (OS). Cases with concurrent expression of MYC and BCL2 showed a lower OS, although the difference did not reach statistical significance. Translocations involving the MYC or BCL2 genes were not detected. The BCL6 gene was frequently translocated, but was unrelated to survival. We conclude that MYC protein expression detected by immunohistochemistry identifies a CNS-DLBCL subset with worse prognosis and may contribute to a more accurate risk stratification of CNS-DLBCL patients.
More information
Navarro JT, Baptista MJ, Morgades M, Tural C, Millá F, Feliu E, Ribera JM

Neoplasms and infections as the main causes of death in patients in complete response to HIV-related non-Hodgkin lymphoma in the combination antiretroviral therapy era: a study out of a series of 146 patients.

Br. J. Haematol. Jul 2013, 162 (2) 289-91. Epub 25 Apr 2013More information
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Current projects

Expression profile and prognostic value of miRNAs in aggressive B-cell Non-Hodgkin lymphomas associated with HIV infection

Project leader:Tomás Navarro
Code:EC11-041
Funding:
Start date:01/01/2012
End date:31/12/2015

Role of Epstein-Barr virus and its miRNAs in the pathogenesis and prognosis of aggressive B-cell lymphomas with or without HIV infection

Project leader:Tomás Navarro
Code:Celgene Spain
Funding:
Start date:01/04/2014
End date:31/03/2017

Grup de Recerca Emergent: Grup de Recerca d'estudi de les neoplàsies hematològiquesdel IJC-Campus Trias i Pujol

Project leader:Francesc Solé
Code:2014 SGR 225
Funding:
Start date:01/01/2015
End date:31/12/2016