Neoplasias linfoides

  • Tomàs Navarro Grup
ICO - Germans Trias i Pujol

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




The research group focuses on the study of lymphomas that affect immunosuppressed patients, both in clinical and genetic aspects. We have made important contributions in this field and our current objective is to unveil genetic and epigenetic characteristics of lymphoid neoplasms that occur mainly in immunosuppressed patients. The purpose is to find markers for a more accurate management of these patients. Furthermore, we aim to implement liquid biopsy as a tool for diagnosis and follow-up of aggressive lymphomas. 


Our research lines are:

-   Genetic studies on of HIV-related lymphomas

Diffuse large B-cell lymphoma is the most frequent type of lymphoma in the HIV-infected population. HIV-infected patients are treated with the same regimens as the HIV-noninfected and similar responses are obtained but their survival is lower due to the higher susceptibility to infections and secondary neoplasms. The biological context of HIV-related lymphomas and the etiopathogenesis may be distinct from HIV-non-infected lymphomas. The disclosure of the transcriptome of HIV-DLBCL and the altered signaling pathways could allow to define prognostic factors, as well as to identify drugs that could revert the abnormal cell functioning. Furtheremor, It would be expected to change the diagnostic tools and prognostic algorithms and to define new and more effective targeted therapies for HIV-DLBCL patients.

-   Liquid biopsy in aggressive lymphomas.

The diagnosis of DLBCL sometimes can be difficult to make it applying all the technics to properly classify it, because not always enough material is obtained from the biopsy. Therefore, a non-invasive method, such as a liquid biopsy could suppose an important advance in the clinical practice for the diagnosis and follow-up of DLBCL. This technique could be useful to diagnose DLBCL earlier, and in a complete and accurate manner than only with tissue biopsy. Moreover, liquid biopsy could be used to unveil treatment resistance, as well as to follow-up the patients and detect lymphoma relapses earlier.

-   Genetic studies on plasmablastic lymphoma.

Plasmablastic lymphoma (PBL) is a rare B-cell lymphoid neoplasm especially affecting immunocompromised individuals. It is an entity with poor prognosis despite treatment. Unlike other lymphomas, the genetic and epigenetic alterations have not been scarcely studied in patients with PBL. In collaboration with Professor Georg Lenz, we have created the “International Consortium of Plasmablastic Lymphoma” a working group to study clinic, genetic and epigenetic landscape of PBL. The identification of abnormalities in the genome, transcriptome and epigenome of PBL will lead to substantial advances in the knowledge of the biology of PBL and it is expected to change the diagnostic tools and prognostic algorithms, finally helping defining the best therapies or to design new therapeutic.

-   Genetic characteristics of Castleman disease.

Castleman disease (CD) is a rare disease, characterized by a non-clonal lymphoid proliferation with an heterogenous clinical course. Some patients have very favorable outcomes whereas other develop highly progressive disease and die within weeks, some developing an aggressive lymphoma. There are few reports on the underling genomic alterations associated with CD and so far, it is unknown the etiology of this disease. We expect to define the transcriptional programs, the cellular signaling pathways and the epigenetic alterations associated with this lymphoproliferative disorder. The results of this research hopefully will identify new CD biomarkers and will support the design of new treatments and target therapies that eventually will improve the prognosis and quality of life of patients with CD.



The Lymphoid Neoplasms Group's main collaborations are:

Department of Pathology, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain

  • Dr. José Luis Mate Sanz
  • Dr. Gustavo Tapia Melendo
  • Ana Maria Muñoz Marmol
  • Carolina Sanz

Department of Hematology, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute (IJC), Institut Germans Trias i Pujol (IGTP), Universitat Autonoma de Barcelona, Badalona, Spain

  • Dr. Josep-Maria Ribera
  • Mireia Morgades

Department Infectious disseases, HIV-Unit, Germans Trias i Pujol Hospital,  Badalona, Spain

  • Dr. José Moltó
  • Dr. Guillem Sirera

IRSI-Caixa, Germans Trias i Pujol Hospital, Badalona, Spain

  • Xavier Martinez Picado 

University of Münster, Münster, Germany     

  •  Dr.Georg Lenz


Selected publications

Frontzek F, Staiger AM, Zapukhlyak M, Xu W, Bonzheim I, Borgmann V, Sander P, Baptista MJ, Heming JN, Berning P, Wullenkord R, Erdmann T, Lutz M, Veratti P, Ehrenfeld S, Wienand K, Horn H, Goodlad JR, Wilson MR, Anagnostopoulos I, Lamping M, Gonzalez-Barca E, Climent F, Salar A, Castellvi J, Abrisqueta P, Menarguez J, Aldamiz T, Richter J, Klapper W, Tzankov A, Dirnhofer S, Rosenwald A, Mate JL, Tapia G, Lenz P, Miething C, Hartmann W, Chapuy B, Fend F, Ott G, Navarro JT, Grau M, Lenz G

Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma.

Nat Commun 31 Ago 2021, 12 (1) 5183. Epub 31 Ago 2021
Plasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients.
Más información
Navarro JT, Moltó J, Tapia G, Ribera JM

Hodgkin Lymphoma in People Living with HIV.

Cancers (Basel) 29 Ago 2021, 13 (17) . Epub 29 Ago 2021
Despite widespread use of combined antiretroviral therapy (cART) and increased life expectancy in people living with HIV (PLWH), HIV-related lymphomas (HRL) remain a leading cause of cancer morbidity and mortality for PLWH, even in patients optimally treated with cART. While the incidence of aggressive forms of non-Hodgkin lymphoma decreased after the advent of cART, incidence of Hodgkin lymphoma (HL) has increased among PLWH in recent decades. The coinfection of Epstein-Barr virus plays a crucial role in the pathogenesis of HL in the HIV setting. Currently, PLWH with HRL, including HL, are treated similarly to HIV-negative patients and, importantly, the prognosis of HL in PLWH is approaching that of the general population. In this regard, effective cART during chemotherapy is strongly recommended since it has been shown to improve survival rates in all lymphoma subtypes, including HL. As a consequence, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential drug-drug interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the optimal treatment of PLWH with HL. In this article the authors review and update the epidemiological, clinical and biological aspects of HL presenting in PLWH with special emphasis on advances in prognosis and the factors that have contributed to it.
Más información
Muncunill J, Baptista MJ, Hernandez-Rodríguez Á, Dalmau J, Garcia O, Tapia G, Moreno M, Sancho JM, Martínez-Picado J, Feliu E, Mate JL, Ribera JM, Navarro JT

Plasma Epstein-Barr Virus Load as an Early Biomarker and Prognostic Factor of Human Immunodeficiency Virus-related Lymphomas.

Clin Infect Dis 15 Feb 2019, 68 (5) 834-843. Epub 29 Jun 2018
Background: Epstein-Barr virus (EBV) has been implicated in lymphomagenesis and can be found infecting tumor cells and in plasma at lymphoma diagnosis, especially in human immunodeficiency virus (HIV)-infected patients. Our aim was to evaluate the usefulness of plasma EBV load as biomarker and prognostic factor in HIV-positive patients with lymphomas. Methods: EBV loads were measured by polymerase chain reaction in plasma samples of 81 HIV-positive patients' lymphomas at different moments: within 1 year before lymphoma diagnosis, at diagnosis, and at complete response (CR). Control samples included HIV-negative patients with lymphomas and HIV-positive patients without neoplasia or opportunistic infections. Results: HIV-positive patients with lymphomas had more frequently-detectable EBV load at lymphoma diagnosis (53%) than either HIV-negative patients with the same lymphoma type (16%; P < .001) or HIV-positive individuals without neoplasia or opportunistic infection (1.2%; P < .001). HIV-positive lymphoma patients with detectable EBV load in plasma at lymphoma diagnosis had statistically significant decrease of EBV load at CR. High EBV load (>5000 copies/mL) at lymphoma diagnosis was an independent negative prognostic factor for overall survival and progression-free survival in HIV-positive patients with lymphomas. Detectable plasma EBV loads identified HIV-positive subjects that would eventually develop lymphoma (area under the curve, 82%; 95% CI: 0.67-0.96). Conclusions: Plasma EBV load can be used as a biomarker and as a prognostic factor in HIV-positive patients with lymphomas. The presence of the EBV load in the plasma of an HIV-positive patient can be an early predictor of lymphoma development.
Más información
Miralles P, Navarro JT, Berenguer J, Gómez Codina J, Kwon M, Serrano D, Díez-Martín JL, Villà S, Rubio R, Menárguez J, Ribera Santasusana JM

GESIDA/PETHEMA recommendations on the diagnosis and treatment of lymphomas in patients infected by the human immunodeficiency virus.

Med Clin (Barc) 13 Jul 2018, 151 (1) 39.e1-39.e17. Epub 19 Ene 2018
The incidence of non-Hodgkin's lymphoma and Hodgkin's lymphoma is higher in patients with HIV infection than in the general population. Following the introduction of combination antiretroviral therapy (cART), the prognostic significance of HIV-related variables has decreased, and lymphoma-related factors have become more pronounced. Currently, treatments for lymphomas in HIV-infected patients do not differ from those used in the general population. However, differentiating characteristics of seropositive patients, such as the need for cART and specific prophylaxis and treatment of certain opportunistic infections, should be considered. This document updates recommendations on the diagnosis and treatment of lymphomas in HIV infected patients published by GESIDA/PETHEMA in 2008.
Más información
Sorigué M, García O, Tapia G, Baptista MJ, Moreno M, Mate JL, Sancho JM, Feliu E, Ribera JM, Navarro JT

HIV-infection has no prognostic impact on advanced-stage Hodgkin lymphoma.

AIDS 19 Jun 2017, 31 (10) 1445-1449.
Classical Hodgkin lymphoma (cHL) is a non-AIDS-defining cancer with a good response to chemotherapy in the combined antiretroviral therapy (cART) era. The aim of the present study was to compare the characteristics, the response to treatment and the survival of advanced-stage cHL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) between cART-treated HIV-positive and HIV-negative patients.
Más información
Show all publications

Current projects

Comprehensive epigenomic analysis of plasmablastic lymphoma: Identifying epigenetic features to improve diagnosis and patient outcomes

Responsable:Tomás Navarro
Fecha de inicio:01/01/2020
Fecha de finalización:31/12/2022

Disclosing the transcriptome of HIV-DLBCL for targeted therapy

Responsable:Tomás Navarro
Fecha de inicio:01/01/2020
Fecha de finalización:31/12/2021

Previous projects

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

Responsable:Tomás Navarro
Fecha de inicio:01/01/2012
Fecha de finalización: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

Responsable:Tomás Navarro
Código:Celgene Spain
Fecha de inicio:01/04/2014
Fecha de finalización:31/03/2017

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

Responsable:Francesc Solé
Código:2014 SGR 225
Fecha de inicio:01/01/2015
Fecha de finalización:31/12/2016

Donación dirigida al estudio de investigación clínica de los linfomas.

Responsable:Tomás Navarro
Fecha de inicio:01/01/2017
Fecha de finalización:31/12/2018

Análisis epigenómico integral del linfoma plasmablástico: identificación de características epigenéticas para mejorar el diagnóstico y el pronóstico de los pacientes

Responsable:Tomás Navarro
Fecha de inicio:01/01/2020
Fecha de finalización:31/12/2020

SGR-2017-2019, Grups de Recerca Reconeguts per la Generalitat de Catalunya. Grup de Recerca IJC Campus ICO-GTP (GRIJC-ICO-GTP)

Responsable:Tomás Navarro
Código:2017 SGR 288-GRC
Fecha de inicio:01/01/2017
Fecha de finalización:31/12/2019