Expression Levels of Jak/Stat Signaling Genes in Newly Diagnosed, Drug Sensitive and Resistant Chronic Myeloid Leukemia Patients

Abstract

JAK/STAT signaling pathway has a role in transmission of information carried by cytokines, from outside of the cell to the nucleus. The system is run by the proteins known as Janus kinases (JAK) located on the cell membrane and STAT proteins acting as signal transducer and activator of transcription. JAK proteins activated by cytokines, phosphorylates and initiates the dimerization of STATs, which become active, move into nucleus and regulate expression of target genes. Previous studies demonstrated that there is overexpression of JAK/STAT genes in various types of cancer. The aim of this study is to examine the relationship between expression levels of JAK/STAT genes and clinical outcome of chronic myeloid leukemia (CML) patients. In this study expression levels of Jak/STAT pathway genes were analyzed in 23 different patients (1 patient responded positively, 1 only imatinib and 1 both imatinib and nilotinib resistant patients, 1 patient lost molecular response, 5 imatinib treated, and 14 newly diagnosed CML patients). The results showed that expression levels of Jak3, STAT1, STAT2, STAT3, STAT4 and STAT5A genes were overexpressed in TKI resistant patients. Expression levels of STAT5B, Jak1, Jak2 and Tyk2 genes were higher in newly diagnosed patients compared to resistant patients while STAT1 was lower in imatinib-treated patients. It was demonstrated for the first time that there is a relation between the clinical outcome of CML patients and expression levels of JAK-STAT genes that could make this signaling pathway a new target for more effective treatment of CML.