Researchers discover cells responsible for resistance to T-ALL treatment

T-cell acute lymphoblastic leukemia (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 tumors before diagnosis.

Tumors 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 analyzing 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 tumor recurrence after treatment are already present at diagnosis, although in almost undetectable numbers. This finding confirms the importance of detecting leukemia early."

Núria López-Bigas, ICREA Researcher

Genome sequencing and bioinformatics analysis

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 tumors (Acute lymphoblastic leukemia, ALL).

"By comparing the primary leukemias in adults and pediatric patients, we have observed that mutational processes are similar between pediatric and adult tumors, and in all subtypes of leukemia," 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."

A project supported by the Asociación Española Contra el Cáncer (AECC)

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.

Source:
Journal reference:

Sentís, I., et al. (2020) The evolution of relapse of adult T cell acute lymphoblastic leukemia. Genome Biology. doi.org/10.1186/s13059-020-02192-z.

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