Acute Leukemia: Discovery of Iron Targeting Molecule May Treat Leukemia Resistant to Conventional Treatments

December 7, 2021

In a study published in the journal Cancer Discovery, Dr Sylvain GARCIAZ, Institut Paoli-Calmettes / CRCM, and his colleagues from the Peter MacCallum Cancer Center in Melbourne and the Institut Curie, describe the therapeutic strategy which allows, by reducing the quantity iron in the mitochondria, to treat leukemia resistant to conventional treatments.

Acute myeloid leukemias (AML) are serious cancers that require heavy treatments based on chemotherapy and stem cell transplantation. A new therapy called venetoclax (Abbvie) recently changed the treatment paradigm for AML. However, leukemia cells develop resistance to this treatment. The targeting of new mechanisms of cell death is a promising strategy to circumvent this resistance. Raphael Rodriguez, a chemist at the Institut Curie, has synthesized a molecule called ironomycin which targets iron in cancer cells causing their destruction.

“We studied, in a collaboration with Mark Dawson’s team at the Peter MacCallum Cancer Center in Melbourne, ironomycin in AML. The results of genomic analyzes using CRISPR Cas-9 technology have shown that ironomycin induces an abrupt cessation of cellular respiration and the death of the cancer cell by a new mechanism, linked to the decrease in the quantity of iron. in the mitochondria. In addition, ironomycin is very effective in eliminating leukemia cells in combination with venetoclax and remains very active in vitro in patients resistant to this treatment, “says Sylvain GARCIAZ.

These preclinical results are important because they pave the way for the use of this molecule or its derivatives in clinical studies. They are part of a comprehensive AML research approach at IPC in partnership with CRCM research teams, which have enabled the discovery of new molecules with therapeutic potential. Early phase clinical research in AML is a priority with 12 innovative drugs being evaluated in clinical trials currently at IPC.

You can read the article here.

Cancer Discovery article references

Pharmacological reduction of mitochondrial iron triggers a non-canonical BAX / BAK dependent cell death

Sylvain Garciaz, Andrew A. Guirguis, Sebastian Müller, Fiona C. Brown, Yih-Chih Chan, Ali Motazedian, Caitlin L. Rowe, James A. Kuzich, Kah Lok Chan, Kevin Tran, Lorey Smith, Laura MacPherson, Brian Liddicoat, Enid YN Lam, Tatianao Canesque, Marian L. Burr, Véronique Litalien, Giovanna Pomilio, Mathilde Poplineau, Estelle Duprez, Sarah-Jane Dawson, Georg Ramm, Andrew G. Cox, Kristin K. Brown, David CS Huang, Andrew H. Wei , Kate Mc Athur, Raphaël Rodriguez, Mark A. Dawson

About the Paoli-Calmettes Institute

Certified by the Haute Autorité de Santé (HAS) in 2015 level A, and accredited as a Comprehensive Cancer Center by the OECI (Organization of European Cancer Institutes) in June 2019, the Paoli-Calmettes Institute is a member of the Unicancer network. The PCI brings together 1,800 medical and non-medical personnel, engaged in the comprehensive care of all cancerous pathologies: research, medical and support care, education and training. The PCI carried out more than 100,000 consultations and welcomed nearly 11,000 new patients in 2020. The PCI is covered exclusively on the basis of social security tariffs, and fee overruns do not apply. are not practiced in the establishment. The PCI has established cooperation with around 20 health establishments in the region.

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