The article, published in the journal Redox Biology by the group of Dr. Manel Esteller, shows that epigenetic changes prevent programmed cell death associated with iron in leukemia and show a new target for treatment with experimental drugs.
All human tumors originating from various tissues share a number of defining properties, including the ability to prevent cell death. Instead, healthy organs induce programmed cell death or apoptosis to balance their size and eliminate damaged cells. There is a specific, physiological cell death called ferroptosis that occurs induced by iron-mediated fat oxidation.
Today, an article published in the journal Redox Biology, the reference journal in the field of free radicals and cancer, by the group of Dr. Manel Esteller, director of the Josep Carreras Leukemia Research Institute (IJC), research professor and president of ICREA. of Genetics from the University of Barcelona, and directed by Dr. Lucas Pontel, shows that epigenetic changes prevent programmed cell death associated with iron in leukemia and shows a new target for treatment with experimental drugs.
“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 iron- and oxidation-induced death.” – says Dr. Esteller and adds – “By studying all these metabolic pathways we realized that in acute lymphoblastic leukemia (ALL) the activity of the FSP1 gene was epigenetically lost, so that these cells were on the precipice of their programmed death . they just needed to be given a boost and that’s what we did by giving them inhibitors of the glutathione pathway, like L-BSO and RSL3, which rapidly induced the death of these malignant lymphocytes, meaning this type of leukemia endures. their tolerance to ferroptosis and when their last lifeline is removed with a drug, these transformed cells die, so this weak spot in acute lymphoblastic leukemia can be precisely explored and treatments customized for this disease, but it can also occur in other cancers There are few clinical trials in oncology with glutathione inhibitors, but perhaps this type of work will arouse interest in the study and development of these pr omitting experimental agents” – concludes the researcher.
In the same line, Dr. Pontel points out that “exploring data from patients with ALL-T and ALL-B, we have detected that FSP1 is under epigenetic control. Thus, by determining the epigenetic status of FSP1 in patients, we could anticipate the success of a therapy based on drugs that induced ferroptosis”.
Source:
Josep Carreras Leukemia Research Institute
Journal reference:
Pontel, LB, et al. (2022) Acute lymphoblastic leukemia requires GSH-dependent ferroptosis defenses to overcome epigenetic silencing of FSP1. redox biology doi.org/10.1016/j.redox.2022.102408.