Expression of JAK/STAT pathway genes using the Real Time Quantitative PCR array technique in multiple myeloma cell lines, before and after the use of potential inhibitors of the pathway

• Grant number: 12/23494-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2013
• End date: December 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Gisele Wally Braga Colleoni
• Grantee: Mariana Bleker de Oliveira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 10/17668-6 - Identification of biomarkers and possible therapeutical targets in B-cell lymphoproliferative disorders, AP.TEM

Abstract

A major change in the treatment of patients with multiple myeloma (MM) occurred with the discovery of new therapeutic agents (thalidomide, lenalidomide and bortezomib). However, MM still remains an incurable disease. Thus, a better understanding of the molecular processes involved in the genesis and progression of this disease is essential for the development of novel drug combinations that achieve more satisfactory results. The constitutive activation of JAK proteins has been demonstrated in MM and other types of cancer, promoting survival and proliferation of tumor cells. In MM, the JAKs might be persistently activated due to the constant stimulation by IL-6. Studies involving JAK inhibitor synthetic molecules showed suppression of STAT3 phosphorylation, a transcription factor activated by IL-6, inducing apoptosis in MM cell lines. These studies suggest that inhibition of the JAK/STAT pathway may be a potential target for the treatment of patients with MM. Therefore, this research project aims: 1) to identify, among the MM cell lines available in our laboratory, those that show a relevant expression of genes JAK1 and TYK2; 2) to evaluate gene expression of the JAK/STAT pathway by real-time quantitative PCR array technique in previously selected MM cell lines; 3) to conduct studies in vitro with the same PCR array platforms and cell lines, now incubated with drugs used in first-line treatment of patients with MM and pan-JAK inhibitors, preferential targets of this research. (AU)