AbstractBackground:
Chronic myeloid leukemia is a clonal myeloproliferative disease which is characterized by bcr/abl translocation. With the emergence of tyrosine kinase inhibitors such as imatinib mesylate, significant improvement has been made in treatment of this disease. However, resistance to tyrosine kinase inhibitor is still a major obstacle. Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor involved in proliferation and survival of several cancers.
STATIP1 (STAT3-Interacting protein-1) is a protein associated with STAT3, which mediates protein-protein interactions and plays an important role in signal transduction, transcription and proteolysis. The aim of this study was to determine the expression of
STAT3 and
STATIP1 in patients with chronic myeloid leukemia treated with imatinib and to identify the possible role of these two genes in
drug resistance in CML patients treated with Imatinib.Aim: In this study, the expression of
STAT3 and
STATIP1 genes in patients with CML and in New cases, MMR, Non-mutated and mutated
Imatinib resistant patients and blastic phase were investigated.Method: The study was conducted on 71 peripheral blood(PB) samples which were collected from patients with CML in different phases of the disease and 10 PB of healthy individuals. After extracting RNA and synthesizing cDNA, expression of
STAT3 and
STATIP1 genes were measured using Real-Time PCR technique. The expression of
STAT3 and
STATIP1 were normalized to ABL control gene. Then expression levels were compared with the control group.Result : The results showed that expression of
STAT3 in the diagnostic stage was significantly higher than normal subjects(p=0.0001) .
STAT3 expression was not significantly different between MMR and the control group.
STAT3 expression was significantly higher in non-mutated and mutated imatinib resistant patients compared to patitents in MMR stage (p=0.0014 & p=0.003 (respectively. This difference was not significant between the two resistant groups. Patients in the blastic phase also had no significant difference in the expression of
STAT3 expression with the control group. Regarding the expression of STATIP1, significant higher expression levels detected in newly diagnosed and Non-mutated and mutated resistant patients compared to the control group. (p=0.03, p=0.002, p=0.01 respectively).Conclusion: Considering the results of this study and the role of
STAT3 in cell proliferation and survival, the targeting of
STAT3 seems to be an effective option in the treatment of resistant patients.