Genetics of hematological malignancies and associated complications
Dr. Manuel Jurado Chacón, Dr. Juan Sainz Pérez
Scientific interest areas
In the past decades, it has become clear that hematological malignancies such as acute leukemias (ALL and AML), monoclonal gammopathies (MGUS and MM), lymphoproliferative disorders (LPD) and myelodysplastic syndromes (MDS) can be caused by a variety of mechanisms, including the inactivation of tumor suppressor genes, activation of oncogenes, and genomic instability. These oncogenic processes arise from the accumulation of many genetic and epigenetic lesions.
Although conventional cytogenetic techniques (karyotyping and fluorescence in situ hybridization) have lead to the identification of large number of chromosomal aberrations and mutations involved in the development and/or progression of hematological malignancies, it is well known that these techniques have some important limitations. The spectacular technological advances in the area of both functional and structural genomics and the exponentially increasing amount of data being generated have shown that many types of genetic variations may affect the risk of developing hematological malignancies. New genomics approaches have contributed to the emergence of an important new dimension into biomedical research with a notorious progress in understanding the structure and function of the human genome as well as its role on cancer biology. Individual genetic variants, either alone or in combination with others, can contribute to change individual cancer risk. However, up to date, only a few genetic biomarkers have been reliably associated with hematological malignancies and disease progression.
For this reason, our research group is focused on the identification of genetic variants (SNPs, indel, CNVs, etc…) associated with hematological malignancies, cancer progression and cancer-related complications such as graft versus host disease and opportunistic infections. In parallel, our group is also aimed at analyzing the interaction of particular genetic variants and cancer risk (gender, obesity, type 2 diabetes, etc…), life-style and environmental factors as well as the characterization of genetic factors contributing to drug resistance. Hypothesis-driven candidate gene and genome-wide association (GWAS) studies along with CGH-A (comparative genomic arrays hybridation) and next-generation sequencing provide an unprecedented opportunity for a comprehensive analysis of the genetic factors involved in hematological malignancies and related traits.
The use of these recently developed methods coupled with genome-wide expression analysis can now help us to identify susceptibility genes for hematlogical malignancies leading to better diagnositics and genotype-guided therapeutic strategies. Likewise, these new technologies have begun to unravel the complex genetic architecture that underlies the diversity of cancers allowing the potential identification of new therapeutic targets.