Effects of Ruxolitinib on Myeloproliferative Neoplasms via the Negative Regulators

Background: We evaluated the JAK2V617F mutation and p-JAK2, SOCS-1, SHP-1 expression in JAK2V617F positive myeloproliferative neoplasms (MPNs) patients and the role of JAK/STAT pathway in human erythroleu-kemia (HEL) cells, which had JAK2V617F mutation.Methods: Protein expression of p-JAK2, SOCS-1, SHP-1 in bone marrow biopsies (BMBs) were detected by im-munohistochemical staining methods. Cell apoptosis and cell cycle were detected by flow cytometry and Caspase 3/7 assay kits.Results: 1. The p-JAK2, SOCS-1, and SHP-1 expressions were significantly different between JAK2V617F positive MPN and control patients (p < 0.01); 2. After being treated for 3 months, the p-JAK2, SOCS-1, and SHP-1 ex-pressions were significantly different compared with newly diagnosed patients (p < 0.01). 3. HEL cell viabilities were significantly different after being treated with different concentrations of ruxolitinib. Ruxolitinib had a signi-ficant effect on the cell apoptosis, viability, and the protein activity of caspase-3 and-7 of HEL cells. 3. The mRNA and protein expressions of JAK2 and the protein expression of p-JAK2 were gradually decreased (p < 0.01, p < 0.05), while the mRNA and protein expressions of SOCS1 and SHP1 were gradually increased (all p < 0.01).(Clin. Lab. 2023;69:xx-xx. DOI: 10.7754/Clin.Lab.2022.220442)

Automated summary

This study evaluated the expression of JAK2V617F mutation and the JAK/STAT pathway in MPN patients and HEL cells. The results showed significant differences in the expression of p-JAK2, SOCS-1, and SHP-1 between JAK2V617F positive MPN patients and controls. After treatment, the expressions of p-JAK2, SOCS-1, and SHP-1 also significantly changed. Ruxolitinib had a significant effect on HEL cell viability and apoptosis.