Lysyl oxidase like-2 (LOXL2) upregulation is associated with key inflammatory signaling pathways in primary myelofibrosis (PMF), according to a recent study presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.
The researchers collected serum samples from patients with PMF and healthy controls. They used polymerase chain reaction, enzyme-linked immunosorbent assay, and enzyme activity assays to quantify LOXL2 mRNA levels, serum protein, and enzyme activity, respectively.
Compared with healthy controls, there was a “significant upregulation” of LOXL2 mRNA, serum protein levels, and enzyme activity in patients with PMF (P<0.001). Patients with high LOXL2 expression were more likely to be classified as high and intermediate-2 according to the International Prognostic Scoring System (IPSS) and Dynamic IPSS (P<0.01). They also showed a higher prevalence of blood blasts, “indicating increased disease severity.”
Gene set enrichment analysis revealed that LOXL2 expression is closely associated with several key inflammatory pathways such as the JAK-STAT signaling pathway, cytokine–cytokine receptor interaction, TNFA pathway, and interferon-gamma response pathway.
Using the CellMiner drug prediction software, the researchers identified dasatinib, everolimus, and simvastatin as promising targeted drugs for LOXL2. They believe they “may offer novel therapeutic strategies” for this patient population.
“The findings suggest that LOXL2 plays a critical role in the pathogenesis of PMF by modulating [key inflammatory signaling] pathways,” the researchers concluded. “The identification of potential targeted drugs for LOXL2, such as dasatinib, everolimus, and simvastatin, opens new avenues for the development of personalized therapeutic approaches in the management of PMF.”
Reference
Lv G, Lv W. LOXL2 as a potential therapeutic target in primary myelofibrosis. Abstract #MPN-752. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.