T-cell acute leukaemia (T-ALL) is a haematological cancer disease, resulting from the malignant transformation of T-progenitor cells [1]. Currently, up to 85 % of the patients achieve 5-year survival rates without relapse with the state-of-the-art procedure. However, if individual cancer cells withstand the initial treatment (persister cells) and the cancer relapses, successive therapies are less effective and the survival rate decreases below 25 % [2]. Drug-resistant cells also pose a serious problem for long-term recovery [3]. Investigations established that this cell type, particularly in a mesenchymal state or close to metastasis, exhibits problems in regulating its inner ROS production and is more susceptible to ferroptosis. This regulated, non-apoptotic cell death is initiated by iron-mediated phospholipid peroxidation through increased reactive oxygen radical production, via various cell metabolism pathways. As a consequence, a small increase in ROS production will push those cells to rapidly enter ferroptosis. By artificially increasing the ROS production in those T-cells, the utilisation of this mechanism to eliminate refractory cancer cells could represent a new generation of cancer therapeutics [4]. The actual chemical “point of no return” responsible for ferroptosis-cell death is yet unknown. It is confirmed that uncontrolled peroxidation of phospholipids plays a crucial role in cell degradation and may be associated with nanoscale hotspots of peroxidised phospholipids causing membrane damage, lipid cross-linking to limit membrane fluidity or impairing membrane integrity by pore formation [4]. The use of atomic force microscopy coupled with infrared spectroscopy (AFM-IR) allows the investigation of spectra-structure correlations in the mid-IR spectral range at nanoscale to achieve chemical identification of these ferroptosis-induced membrane changes. Investigations were performed on an immortal cell line (Jurkat) spiked with two known ferroptosis inducing reagents (APR-246, RSL3) to initiate cell death. The paraformaldehyde-fixed cells were analysed for the appearance of carbonyl ester bands of various oxidized lipid peroxidation end products in the membranes. A better understanding of the degradation processes caused by ferroptosis at the nanoscale could contribute to a better perception of this outstanding mechanism and the development of future therapeutics. [1] P. Van Vlierberghe and A. Ferrando, ‘The molecular basis of T cell acute lymphoblastic leukemia’, J. Clin. Invest., vol. 122, no. 10, pp. 3398–3406, Oct. 2012, doi: 10.1172/JCI61269. [2] E. A. Raetz and D. T. Teachey, ‘T-cell acute lymphoblastic leukemia’, Hematology, vol. 2016, no. 1, pp. 580–588, Dec. 2016, doi: 10.1182/asheducation-2016.1.580. [3] R. Rodriguez, S. L. Schreiber, and M. Conrad, ‘Persister cancer cells: Iron addiction and vulnerability to ferroptosis’, Molecular Cell, vol. 82, no. 4, pp. 728–740, Feb. 2022, doi: 10.1016/j.molcel.2021.12.001. [4] X. Jiang, B. R. Stockwell, and M. Conrad, ‘Ferroptosis: mechanisms, biology and role in disease’, Nat Rev Mol Cell Biol, vol. 22, no. 4, pp. 266–282, Apr. 2021, doi: 10.1038/s41580-020-00324-8.