The Significance of Ubiquitin-Proteasome Pathway in Glucocorticoid Resistance Development in Acute Lymphoblastic Leukemia

ALL is the most common malignancy in childhood. Presently, approximately 20% of patients do not respond to treatment due to the resistance of leukemia blasts. Response to GCs is considered as the strongest independent factor in predicting ALL patients outcome. Therefore, identification of GCs resistance markers are the beneficial tools for improvement of prognostic strategies in ALL.
In this experimental study, the protein-protein interaction network of fourteen significant down or up-regulated proteins in the proteome of human lymphoblastic cell treated with prednisolone and dexamethasone were analyzed by using the STRING online database.
By using proteomics methods, fourteen down or up-regulated proteins, SRSF3, CNBP, VDAC1, SNX3, PFDN6, PSMB2, STMN1, PPP4R4, DUT, CAPZA1, CAPZB, PNP, CLIC1 and PSME1 were recognized in both the sensitive and resistant GC cell lines. Correlation between these proteins were analyzed by using the STRING database.
Conclusions : Overall, the findings showed that the Ubiquitin-Proteasome pathway plays a pivotal role in inducing resistance to GC in ALL. Therefore, the study of key controlling proteins in this pathway can play an important role in clarifying the mechanisms of induction of resistance to GC and consequently the prognosis of the disease.