Translational Immunomics in Hematological Neoplasms

"Our goal is to develop new treatments for patients with hematological tumors by understanding the pathogenesis of the disease."


Myeloid diseases are disorders of the blood or hematopoietic stem cells (HPCs) of the myeloid lineage. Alteration in cell maturation or abnormal proliferation of these cells leads to infections, anemia, bleeding and cancers such as leukemias. These diseases commonly affect people between 65 and 70 years of age, and their prevalence is expected to increase in the coming decades.

Research progress in recent years in understanding the molecular basis of many hematologic cancers has translated into clinical benefit for the patient. However, among these myeloid neoplasms, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) are two very aggressive diseases that lack effective treatment.

For this reason, our Translational Immunomics in Hematological Neoplasms Group at Cima focuses on the study of the mechanisms of transformation of these two major diseases. Our research includes the identification of genetic and epigenetic changes (cellular reactions that change the functions of genes, without being part of the DNA), the development of new drugs that can be molecular targets in patients, and resistance to therapy determined by the tumor microenvironment.

We work in close collaboration with other researchers in the Hematology-Oncology Program at Cima and clinicians at the Clínica Universidad de Navarra with a primary focus on translational research and clinical trials exploring innovative treatments for these diseases.

Our program is linked to the Centro de Investigación Biomédica en la Red de Cáncer (CIBERONC) of the Instituto de Salud Carlos III (ISCIII), as well as to numerous academic and research centers nationally and internationally.

Dr. Bruno Paiva


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   Research profile

Objectives of the Research Group
in Translational Immunomics in Hematological Neoplasms

We cover the study of multiple myeloma and other monoclonal gammopathies through a cross-sectional investigation.

To understand the mechanisms involved in the transformation of healthy plasma cells into pre-malignant and cancerous cells.


Identify the plasma cell clone responsible for dissemination, resistance, and relapse, by studying circulating tumor cells (CTC) and minimal residual disease (MRD).

Identify extreme phenotypes: cure vs. resistance

To develop animal models of multiple myeloma that reproduce its complexity and heterogeneity and allow the design of new treatments.

Identification of metabolic vulnerabilities in these diseases.

To define the role of the immune system and the microenvironment in the pathogenesis of multiple myeloma and acute leukemia, and in their drug resistance.

Developing strategies to reverse tumor resistance and finding highly accurate biomarkers to monitor treatment efficacy.

To develop clinical trials that can improve the treatment of multiple myeloma (CAR-T therapies).

To understand the implication of alterations in the transcriptome and epigenome in the development and progression of multiple myeloma and acute leukemia.

To develop new compounds directed against epigenetic mechanisms with activity in multiple myeloma cells.



New therapeutic alternatives for the treatment of multiple myeloma

Proteosome inhibitors, which induce cell death; immunomodulators that stimulate our immune system and monoclonal antibodies that are able to detect an antigen of the tumor cell in order to destroy it, are the main lines of our research.

Lines of research

PI: Bruno Paiva


  1. To develop a complete immunophenotypic characterization of tumor cell precursors (including single cell level analysis) in healthy individuals of advanced age and in premalignant stages of MM (MGUS and smoldering MM) and AL to discover new markers involved in malignant transformation.
  2. To study the role of circulating tumor cells (CTCs) and common progenitor cells (CPCs) in the dissemination from benign to malignant stages.
  3. To discover the role of the immune system as a driver and Achilles heel of malignant transformation.

PI: Patricia Maiso


  • To compare the genomic profile of bone marrow mesenchymal stromal cells (MSCs) from healthy donors with those at diagnosis (in AL and MM).
  • To investigate the genomic profile and biomarkers of BMMSCs at the time of diagnosis (AL and MM), at the time of MRD and at the time of relapse in both diseases.

PI: Xabier Agirre

Our general objective is to study and to know in depth both the complete transcriptome (especially the one referring to long non-coding RNAs (lncRNAs)), the altered epigenome and the aberrant metabolism of tumor plasma cells of monoclonal gammopathy of uncertain significance and multiple myeloma. This objective pursues the aim to better understand the biology of the disease and to detect new targets for the development of new therapeutic strategies for the treatment and improvement of the quality of life of these patients.


  • Analysis of the complete transcriptome of lncRNAs of multiple myeloma tumor cells, in the context of the humoral immune response, and functional study of lncRNAs altered in this disease.
  • Design and validate new RNA-based therapeutic strategies for the treatment of multiple myeloma.
  • Analysis of the epigenome of the tumor plasma cell of monoclonal gammopathy of uncertain significance and multiple myeloma, both in mouse models and primary samples, and the functional study of its alteration in this disease.
  • Detection and functional studies on essential and synthetic lethal metabolic genes in multiple myeloma.
  • Synthesize and validate new small molecules directed against genetic and metabolic targets for the treatment of multiple myeloma.

PI: Bruno Paiva


  • Define the genome and proteome of MRD vs diagnostic clones to understand the molecular signature of ultra-chemoresistant cells that allow them to resist therapy.
  • To understand the relevance of molecular and immunological signatures of MRD clones on patient survival.
  • Optimize MRD and liquid biopsy strategies to monitor treatment efficacy: i) is sustained MRD negativity a surrogate for operational cure; ii) role of immune surveillance in MRD+ patients; iii) role of immune surveillance in MRD+ patients.

PI: Bruno Paiva y Patricia Maiso


  • Analyze the mechanisms of action and synergy of efficacy in tumor cells and immune system.
  • Implement new generation biomarkers to monitor clinical trials.

PI: José Ángel Martínez Climent


We have generated a series of experimental models in genetically modified mice that recapitulate the main biological and clinical features of multiple myeloma (MM), including the progressive development of a precursor phase of the disease in the bone marrow (resembling monoclonal gammopathy of uncertain significance MGUS) that eventually progresses to clinically symptomatic MM.

These experimental models include the main genetic lesions detected in patients with MM, allowing them to be sub-classified into genetic risk groups (standard, intermediate, and high). Our preliminary data show that malignant plasma cells in mice are very similar to cells from patients with the disease, both phenotypically and molecularly, in the different genetic risk subgroups.

We also observed that the bone marrow microenvironment in which disease develops in mice includes a progressive increase in infiltrating CD8 T lymphocytes, with effector phenotype and PD-1 expression. In this context, depletion of these T subpopulations accelerates the development of MM, suggesting a role of the immune system in the development of the disease.

The overall objective of the present project is to define the immune biology and the response to immunotherapy strategies in the different genetic risk subgroups in MM, and is based on the preliminary results obtained through the development and characterization of experimental murine models.

In the present project we will continue the study of such models using high resolution cellular and molecular analysis techniques, which have been developed in our hemato-oncology department, and the results will be analyzed with integrative methods of computational biology.

The specific objectives are the following:

  1. Determine the molecular mechanisms that converge to promote the progressive transformation of plasma cells in the different experimental models.
  2. Characterize the role of the immune system in the progressive transition between MGUS and MM phase in different experimental models.
  3. To evaluate the response to different combinations of targeted therapeutic agents and immunotherapy in the experimental models.
  4. Characterize the mechanisms of therapeutic response and resistance to immunotherapy in the tumor plasma cell and bone marrow microenvironment.
  5. The mouse results will be analyzed in the context of human pathology, with the aim of defining the immune biology of MM development with unprecedented resolution, which will hopefully contribute to the experimental design of future clinical trials of MM patients.

Meet the research team

Scientific activity of the Translational Immunomics in Hematological Neoplasms a Research Group

Regenerative Medicine


Cima Principal Investigator: Xabier Aranguren López
Funder: Gobierno de Navarra