Signal transducer and activator of transcription 3 (STAT3) gene polymorphisms are associated with treatment outcomes in acute myeloid leukemia

Abstract

The results of this study suggest that the GG genotype in rs9909659 might confer increased resistance to standard chemotherapy.

STAT3 rs3816769 polymorphism correlates with gene expression level and may predispose to nonsmall cell lung cancer: a preliminary study

“…Patients were divided into groups according to their smoking habits: the period of tobacco addiction and the amount of cigarettes smoked -the latter was presented as pack years and was calculated according to the NCI Dictionary of Cancer Terms (1 pack year is equal to smoking 20 cigarettes per day for 1 year). 29 dnA extraction and snP genotyping Two SNPs in the STAT3 gene, rs744 166, and rs3 816 769, have been selected based on the previously published reports regarding their associations with lung cancer risk 25 and a significant role in inflammation. 26 Genomic DNA from patients and the control group was isolated from blood samples using Qiagen QIAamp DNA Mini Kit, according to the manufacturer's procedure.…”

STAT3 polymorphisms may predict an unfavorable response to first‐line platinum‐based therapy for women with advanced serous epithelial ovarian cancer

“…rs4796793 was not a top-ranked SNP in our dataset. In patients with acute myeloid leukemia, 21 rs9909659 was associated with increased resistance to daunorubicin chemotherapy and was marginally associated ( p = 0.049) with an incomplete response to platinum-based therapy among women with EOC in our dataset.…”

“…Strengths of our study include the novelty of the topic area, the multitiered genomic evaluation and the larger sample size compared to other studies that reported associations between CSC-related SNPs and response to therapy. 16,17,[19][20][21] Another strength is the relatively homogeneous population of women treated for their diagnosis of advanced serous EOC, though it has been recognized that there is vast diversity in the combinations of platinum-and taxane-based adjuvant treatments that these patients have endured. 47 We recognize the possibility of false-positive results and the importance of attempting to replicate these findings, and plan to do so once denser genotype and imputed data and detailed clinical follow-up data become available from a large, independent cohort of EOC cases genotyped by the international Ovarian Cancer Association Consortium (OCAC).…”

“…10 Moreover, high expression levels of several of these markers have been associated with recurrent disease, chemoresistance and poor survival. [11][12][13][14][15] Germline variants in the CSC genes CD44, CD133 and STAT3 have been linked to clinical outcomes in patients with localized gastric adenocarcinoma 16 and colon cancer, 17 metastatic colorectal cancer 18 and metastatic renal cell carcinoma 19,20 and acute myeloid leukemia, 21 respectively. Variants in CSC genes may also alter gene expression and/or activity in EOC tissues and ultimately contribute to clinical outcomes, yet no published investigations of this topic area exist.…”

Roles of STAT3 in leukemia (Review)

“…Moreover, Adamaki et al (118) discovered that 8 out of 14 childhood patients with ALL, in which STAT1 and STAT3 were expressed at lower levels on day 33, were relapse-free with a high survival rate, indicating that STAT3 gene upregulation is a poor predictor of the clinical prognosis of childhood ALL. Furthermore, Zhong et al (119) investigated the association between genomic polymorphisms of STAT3 and AML patient response to chemotherapy in a Chinese population, and found that there were strong associations between unfavorable cytogenetics, partial remission (and even no remission) and GG genotype frequency in rs9909659, which suggested that the STAT3 GG genotype in rs9909659 may confer an enhanced resistance to standard chemotherapy, and predict an unfavorable prognosis. Besides, it has also been reported that constitutive STAT3 activation is associated with the shortest disease-free survival in AML, and the subgroup of AML patients, which expressed STAT3β and showed constitutive activity of STAT3, experienced a particularly poor outcome (92).…”