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Drug sensitivity linked to leukaemia susceptibility

The article was published in the journal Redox Biology. 

Leukaemia is a type of blood cancer that affects blood cells in your bone marrow, usually white blood cells.

The team led by Dr. Lucas Pontel and including Dr. Manel Esteller, Director of the Josep Carreras Leukemia Research Institute (IJC), ICREA Research Professor, and Chairman of Genetics at the University of Barcelona, has demonstrated that epigenetic changes prevent iron-associated programmed cell death in leukaemia and reveal a new target for treatment with experimental drugs.

To put it another way, this particular type of leukaemia is on the brink of its ability to tolerate ferroptosis, and when a medicine is used to cut off their last hope of survival, the altered cells die.

“Leukemia cells avoid dying because they have two floats, the metabolism of the biomolecule called glutathione and the FSP1 gene that acts as a shield against this death induced by iron and oxidation.” — comments Dr. Esteller and adds — “Studying all these metabolic pathways we realized that in acute lymphoblastic leukemia (ALL) the activity of the FSP1 gene was epigenetically lost, so these cells were on the edge of the precipice of their programmed death. We only needed to give them a boost and that is what we did by administering them inhibitors of the glutathione pathway, such as L-BSO and RSL3, which rapidly induced the death of these malignant lymphocytes.

In order to develop precise and individualised treatments for acute lymphoblastic leukaemia, this weak area can be investigated, albeit it may also exist in other tumours.

Although glutathione inhibitor clinical trials are scarce in oncology, the researcher hopes that his or her discovery may spark interest in the investigation and advancement of these intriguing investigational medicines.

In a similar vein, Dr. Pontel notes that they discovered FSP1 is under epigenetic control by analysing data from T-ALL and B-ALL patients.

As a result, by assessing the FSP1 epigenetic status in patients, we may be able to predict how well a therapy based on medications that promote ferroptosis will work.

Drug sensitivity linked to leukaemia susceptibility

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