Translational Genomics of Blood Cancers

Our translational group aims at establishing proposals for prevention strategies for blood cancers and and solid tumors to prevent relapse and disease progression. We base our strategy on risk and prognostic profiles that integrate different biomarkers from the genomics, epigenomics, transcriptomics, metabolomics and proteomics fields, in combination with microbiome, environmental and lifestyle factors along the natural history of the malignant disease. The long-term treatment of blood cancers (including stem cell transplantation when it happens) is usually linked to higher health care costs in comparison with solid cancers and the relapses of blood cancer patients are frequently associated with high treatment costs, as well as the indirect expenses of lost productivity and loss of quality of life. Furthermore, other costs that can be prevented by improving risk stratification are those of office-based visits and medication that are dispensed to patients who will not benefit from them, or avoidable expenditures for patients who could have been diagnosed with blood cancer earlier. By developing better risk and prognostic stratification strategies, our group aims to identify patient groups at low or high risk for progressive disease. If we are able to reach this ambitious aim, we might then develop tailored surveillance programmes to reduce health care costs and improve patient well-being and survival rates.

Considering all the above, our group has the following objectives:

To develop and implement personalised disease prevention programmes for blood cancers including multiple myeloma (MM), chronic lymphoid leukemia (CLL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), myeloproliferative disorders (MPNs), and chronic myelomonocytic leukemia (CMML). These programmes are designed considering the molecular characteristics of individuals (genomics, epigenomics, transcriptomics, metabolomics, and proteomics), complemented by microbiome and exosome data and environmental and lifestyle factors. This approach could provide standardized methods or individualised tools for prevention and risk stratification, improve early diagnosis of blood cancers (particularly for aggressive subtypes with fast disease progression and shorter survival periods), and open new avenues for the design or more efficient treatments. In order to build these prevention programmes, we are also considering the molecular information provided by individuals suffering from different precursor conditions such as monoclonal gammopathy of uncertain significance (MGUS) and monoclonal B-celllymphocytosis (MBL).

To integrate different OMICs (genomics, epigenomics, transcriptomics, metabolomics, and proteomics) for the prediction of relapse, disease progression, and overall patient survival. This combined approach will help identifying patients that would be prone to experience relapse and, therefore, would benefit from a sustained monitoring. Additionally, this study will be instrumental in tailoring specific therapies to individual patients according to their OMICs profiles, in order to increase individuals who will benefit from treatment.

To functionally characterize susceptibility and prognostic biomarkers for blood cancers. Given the known implication of host immune responses and inflammation in blood cancer onset, disease progression and efficacy to immunotherapeutic agents, we are also working to assess whether those biomarkers associated with higher risk to develop blood cancers, disease progression and patient survival correlate with cytokine expression quantitative trait loci (cQTL) data from in vitro stimulation experiments, absolute numbers of blood-derived cell populations, and circulating concentrations of multiple immunological proteins and steroid hormones.

Main research lines:

• Longitudinal and multi-OMIC approaches for blood cancers.
• Genomics of premalignant monoclonal B-cell disorders: MGUS and MBL.

Secondary research lines:

• Genetics basis of susceptibility to infections in blood cancers (COVID-19 and fungal infections)
• Genomics of autoimmune diseases: Progression to blood cancers
• Genomics of solid tumours: colorectal, pancreatic and prostate cancers

The major impact expected of our research lines is the identification and validation of risk stratification profiles in blood cancers. We aim at promoting primary and secondary prevention strategies for disease onset and disease progression. Through different research projects we are also attempting to increase awareness of the value of OMICS-based stratification and promote collaboration, training and multidisciplinary cooperation among outstanding international groups to increase research capacity.

Our group is involved in several international consortia, including CRuCIAL (Chronic Lymphocytic Leukaemia), NuCLEAR (Acute Myeloid Leukemia), aspBIOmics (invasive fungal infections), IMPULSE (Myeloproliferative neoplasms), MIRACLE (Myeloproliferative neoplasms), and REPAIR (Rheumatoid Arthritis and Ankylosing Spondylitis).

Our group also participates as active member in other international consortia such as CIBERESP (Consortium for Biomedical Research in Epidemiology and Public Health), IMMEnSE (Multiple Myeloma), InterLymph (Lymphoma), GECCO (Colorectal Cancer), DACHS (Colorectal Cancer), PANDORA (Pancreatic Cancer), PRACTICAL (Prostate Cancer), and several cooperative groups such as GESMD (Spanish group of Myelodysplastic Syndromes).