T-cell acute lymphoblastic leukaemia (T-ALL) is a cancer of the blood that affects mainly children, but also less frequently adults. In adults, although the response to treatment might be initially positive, relapses are common and have a poor prognosis.
A collaborative project between IRB Barcelona’s Biomedical Genomics lab, headed by ICREA researcher Núria López-Bigas, Anna Bigas’ group at the Hospital del Mar Medical Research Institute (IMIM-Hospital del Mar), and Josep Maria Ribera’s lab at the Josep Carreras Leukaemia Research Institute (IJC) has discovered that the cells responsible for resistance to T-ALL treatment in adults are already present in the tumours before diagnosis.
Tumours can be understood as cell populations that evolve. Cancer cells acquire mutations that confer an advantage over other cells, for example, allowing them to divide faster, or in this particular case, to be resistant to treatment.
“After analysing various samples from 19 adult patients, we have been able to describe the evolution of the disease and we have concluded that the cells responsible for tumour recurrence after treatment are already present at diagnosis, although in almost undetectable numbers,” says López-Bigas. “This finding confirms the importance of detecting leukaemia early,” she adds.
To carry out this work, the group of researchers sequenced the genome of 19 patients at the time of diagnosis and during treatment and relapse, and compared the information obtained with a database of 238 patients (adults and children) affected by similar kinds of tumours (Acute lymphoblastic leukaemia, ALL).
“By comparing the primary leukaemias in adults and paediatric patients, we have observed that mutational processes are similar between pediatric and adult tumours, and in all subtypes of leukaemia,” says Inés Sentís, co-first author of the study together with Santiago González and PhD student in the Biomedical Genomics lab. “But specific genetic alterations, responsible for malignancy, differ between the different forms of this particular disease.”
This work is part of the collaboration group (AECC-funded project) led by Anna Bigas, which was set up to explore the resistance mechanisms of T-ALL in adults and children and has been supported by the AECC since 2016.
“This investigation is possible thanks to the collaboration of clinical, basic and computational laboratories, as in this case. Our next challenge is to identify the cells responsible for relapse upon diagnosis,” says Anna Bigas.
This group was established for 5 years and is formed by the labs run by Josep María Ribera, head of the Haematology Service at ICO Badalona (Germans Trias i Pujol Hospital) and head of the ALL Research Group at IJC, Anna Bigas, coordinator of the Stem Cell and Cancer research group at IMIM-Hospital del Mar, and Núria López-Bigas, who leads the Biomedical Genomics lab at IRB Barcelona.
Reference article:
Sentís I, Gonzalez S, Genescà E, García-Hernández V, Muiños F, Gonzalez C, López-Arribillaga E, Gonzalez J, Fernandez-Ibarrondo L, Mularoni L, Espinosa L, Bellosillo B, Ribera JM, Bigas A, Gonzalez-Perez A, Lopez-Bigas N.
The evolution of relapse of adult T cell acute lymphoblastic leukemia
Genome Biol. 2020 Nov 23;21(1):284. doi: 10.1186/s13059-020-02192-z.
Created in 2005 by the Generalitat de Catalunya (Government of Catalonia) and University of Barcelona, IRB Barcelona is a Severo Ochoa Centre of Excellence, a seal that was awarded in 2011. The institute is devoted to conducting research of excellence in biomedicine and to transferring results to clinical practice, thus improving people’s quality of life, while simultaneously promoting the training of outstanding researchers, technology transfer, and public communication of science. Its 27 laboratories and seven core facilities address basic questions in biology and are orientated to diseases such as cancer, metastasis, Alzheimer’s, diabetes, and rare conditions. IRB Barcelona is an international centre that hosts 400 employees and more than 30 nationalities. It is located in the Barcelona Science Park. IRB Barcelona forms part of the Barcelona Institute of Science and Technology (BIST) and the “Xarxa de Centres de Recerca de Catalunya” (CERCA).
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