"We develop molecules and therapeutic strategies especially in leukemias and B-lymphomas that do not have satisfactory treatments."
DR. JOSÉ ÁNGEL MARTÍNEZ CLIMENT SENIOR RESEARCHER. LYMPHOPROLIFERATIVE SYNDROMES RESEARCH GROUP
The research of the Lymphoproliferative Syndromes Group at Cima focuses on diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL) and Waldenstrom's macroglobulinemia (WM).
We approach these hematological malignancies with a multidisciplinary approach thanks to the close collaboration between basic and clinical researchers at Cima and the Clínica Universidad de Navarra.
Lymphoproliferative syndromes (LPS) are a group of hematological malignancies characterized by the proliferation of neoplastic mature lymphocytes. Among SL, B-cell non-Hodgkin's lymphomas (B-NHLs) account for 40% of all hematologic malignancies and comprise a diverse group of more than 20 unique subtypes that are routinely classified according to clinical, histopathologic, and genetic features.
Biological heterogeneity within each lymphoma subtype is hindering the successful demonstration of novel targeted therapies in clinical trials and, therefore, advances in such therapeutic strategies will require a better understanding of the fundamental biology of each lymphoma entity in order to define optimal drug combinations for specific patient groups. In addition, interactions between lymphoma cells and microenvironmental cells in the lymph node, bone marrow and other lymphoid tissues have also been found to be critical in the pathogenesis of lymphoma and, consequently, such tumor cell-microenvironment dependencies are expected to reveal novel therapeutic interventions.
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Objectives of Lymphoproliferative
Syndromes Research Group
Our priority is to develop new therapies that offer solutions to patients
To determine the cellular and molecular features underlying B-cell lymphoma and plasma cell tumor development in genetic mouse models, defining similarities with human diseases.
To evaluate the in vivo preclinical antitumor efficacy of standard of care treatment of the patient alone and in combination with other immunotherapeutic and targeted agents.
Dissect mechanisms of therapeutic response and resistance based on tumor cell and microenvironmental characterization.
NEW THERAPEUTIC COMBINATIONS
Immunotherapy and molecularly targeted drugs
With advances in the preclinical and clinical development of new agents targeting B-NHL, there is a clear need to prioritize combinations of these drugs and immunotherapy strategies.
Our group is working on testing these strategies in genetically engineered immunocompetent mouse models (GEIMMs) that recapitulate the complex heterogeneity of B-NHL with the goal of achieving predictive guidance for patient treatment.
Lines of research
PI: Dr. Martínez-Climent y Dr. Roa
- To elucidate the role of genes commonly altered in B-cell lymphoproliferative syndromes by introducing these genetic alterations in mouse models at different B-cell stages (from immature B cells in bone marrow, to mature cells in germinal centers or lymphoid tissues).
- To investigate the role of the tumor microenvironment in these immunocompetent murine models, combining analysis of tumor and non-tumor cells during disease progression.
- To integrate the molecular and cellular characterization of tumors in GEMs models through the analysis by advanced molecular techniques of samples obtained from patients with these pathologies.
PI: Dr. Martínez-Climent y Dr. Roa
- Design and test new therapeutic approaches directed against the different alterations produced in genetically modified mice, as well as the study of altered molecular pathways in human and murine tumors.
- Maximize the use of immunocompetent mouse models to explore mechanisms of action, therapeutic resistance, and synergistic potential of drugs and immunotherapy for the treatment of lymphoproliferative syndromes.
Meet the research team
Scientific activity of the
Lymphoproliferative Syndromes Research Group
Latest scientific publications
- Preneoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma Jan 21, 2022 | Magazine: Science Advances
- Endogenous retroelement activation by epigenetic therapy reverses the Warburg effect and elicits mitochondrial-mediated cancer cell death May 1, 2021 | Magazine: Cancer Discovery
- Frequent mutations in the amino-terminal domain of BCL7A impair its tumor suppressor role in DLBCL Oct 1, 2020 | Magazine: Leukemia
- B-cell leukemia transdifferentiation to macrophage involves reconfiguration of DNA methylation for long-range regulation Apr 1, 2020 | Magazine: Leukemia