Genetic sequencing to fight leukemia
José Pichel Andrés/DICYT The European Commission has launched a project under the Seventh Framework Programme in which a dozen partners from universities and companies work together in order to sequence the genome of leukemia patients; the main objective is to design tailored and more effective therapies. The study is to be conducted between 2013 and 2015 and a research team from Salamanca is participating as the only Spanish partner.
Next Generation Sequencing for Targeted Personalized Therepy of Leukemia is the name of the project that “uses new massive sequencing techniques” to determine the most common genetic changes of the disease; its main goal is to develop therapies to fight leukemia, as DiCYT was told by Jesús María Hernández from de Department of Hematology of the Hospital Universitario de Salamanca and the Centro de Investigación del Cáncer (a cancer research center).
This consortium, that has nearly six million Euros to carry the project out over the next three years, is led by the Università di Bologna (Italy) working hand in hand with the Università di Torino (Italy), the Univertität Ulm (Germany), the Masarykova Univerzita (the Czech Republic), the KU Leuven (Belgium) and the Universidad de Salamanca (Spain), as well as companies from Italy, Switzerland and Germany. The scientists from Salamanca are responsible for selecting suitable patients to be part of the study.
The Spanish partner got involved thanks to its extensive experience in this research area, since it belongs to the European Leukemia Net, which brings a thousand researchers together. Therefore, Jesús María Hernández Rivas and his team were part of a project called Microarray Innovations in Leukemia (MILE), which proposed an improved diagnosis of leukemia taking into account RNA microarrais (Ribonucleic acid chips). However, the current project is based on both DNA and RNA sequencing of patients with leukemia.
The Spanish group has also co-led a project called European Genomics and Epigenomics Study on MDS and AML (EuGESMA) that has developed new methods for genetic and epigenetic research used for myeloid leukemia studies.
Thanks to these and other projects, “we can share technology and findings and we have been able to secure links with researchers in other countries”, the expert stated. All projects have focused on the same area: “improving the diagnosis and treatment for leukemia”.
Methods have changed. The human genome sequencing have opened up additional research possibilities reflected, for instance, in the international consortium created for cancer genome studies (International Cancer Genome Consortium, ICGC), a global project sequencing the entire genome of 500 patients from each of the fifty most common cancers and Spain has been working on chronic lymphocytic leukemia (the most common type of leukemia).
The current challenge is to bring findings into practice and “to determine the mutations of these conditions to treat them the same way”. In order to do so, researchers must resort to bioinformatics and interpret a great deal of information provided by new massive sequencing techniques. So far, scientists have focused on the exome (the portion of the gene producing proteins), but they know the rest of the genome is also very important, especially because of findings in the ENCODE project. “Perhaps, we are to focus on the exome because the rest exceeds our scope”, Hernandez Rivas admits, “but our next step is to analyze the whole genome and the transcriptome of tumors”.
Characteristics of the Disease
When analyzing in parallel a normal DNA sample and a sample with leukemia, “features found in the second and not is the first one will be considered characteristics of the disease”, the expert states. This is the way to know how many mutations are part of leukemia, a fairly large number in every patient, but much lower than those in the most common neoplasms such as lung or breast cancer.
During this process it is very important to establish whether mutations are clearly related to the onset of the disease or whether they are “mere companions” of the notable ones, which is difficult to do because tumor cells, by definition, have genetic instability. “Their repair mechanisms get damaged and, consequently, mutations are more likely to arise than in any other type of cell”, he explains.
In chronic lymphocytic leukemia, “the most common mutated gene appears only in 12% of patients”, in spite of the fact that tumors do not contain a single mutation explaining so; that is, “we are probably naming something that is actually a group of many diseases developing similarly”.
Therefore, massive sequencing will allow scientists to change phenotypic diagnoses for molecular diagnoses and will also allow them to change treatment approaches towards genetic disorders, upgrading their efficacy.