Patients with chronic lymphocytic leukemia (CLL) may benefit from the use of a ferroptosis molecular subtype-related signature tool for determining the likelihood of response to chemotherapy as well as prognosis, according to research published in BioMed Research International.
Ferroptosis, a process first discovered in 2012, is the death of cells due to the iron- dependent accumulation of lipid hydroperoxides. Previous work suggests that this process may allow the elimination of leukemic cells without damage to normal cells.
It is, however, unknown the degree to which ferroptosis may play a role in the CLL setting — the most common leukemia, which is generally considered incurable. The heterogeneous presentation and development of CLL, furthermore, necessitates useful prognostic tools for determining risk groups.
Previous work has suggested that ferroptosis-related genes may be predictive of clinical outcome in the setting of other cancers. For this study, researchers aimed to establish a link between ferroptosis-related genes and prognosis, as well as likelihood of response to chemotherapy, in CLL.
The researchers obtained patient data from the International Cancer Genome Consortium; data from 300 patients were used as a training cohort. Overall, 14 of 110 ferroptosis-related genes (FRGs) were determined to have prognostic value. Patients were then classified by survival; most noted FRGs were highly expressed among those with improved survival.
The researchers next developed an 8-FRG signature risk tool; this included TP63, STEAP3, NQO1, ELAVL1, PRKAA1, HELLS, FANCD2, and CDKN2A. Based on analysis from this tool, patients were included in a high- or low-risk group. Using an external cohort, researchers further validated risk partitioning using this tool.
Further analysis suggested that patients in the low-risk group were more likely to respond to common CLL drugs, including fludarabine, cyclophosphamide, and ibrutinib.
“This eight-gene signature is strongly associated with [survival] in CLL patients and might serve as a potential prognostic biomarker for clinical use,” the authors wrote. “In future work, the development of personalized treatment strategies for each patient will be an essential topic.”
Gong H, Li H, Yang Q, et al. A ferroptosis molecular subtype-related signature for predicting prognosis and response to chemotherapy in patients with chronic lymphocytic leukemia. Biomed Res Int. 2022;2022:5646275. doi:10.1155/2022/5646275