Despite recent advances in treatment strategies, multiple myeloma (MM) still tends to be a hard-to-treat hematological cancer. Bone marrow (BM) microenvironment components have a critical role in tumor survival and drug resistance that appears in a vast majority of patients. To improve the prognosis of myeloma patients it is essential to overcome drug resistance. It has been demonstrated that MM cells in the BM niche are much less sensitive to chemotherapeutic agents. This type of drug resistance is termed cell adhesion mediated drug resistance (CAM-DR). Integrin α4β1 controls myeloma cell trafficking to BM compartment and it has been implicated in CAM-DR. We propose to identify miRNAs altered in α4β1 mediated adhered cells and once identified, study the possible role of these miRNAs in MM progression using in vitro and in vivo approaches. Bortezomib (BTZ) is the most common drug used in MM treatment. Using different MM cell lines we will develop BTZ resistance clones, to elucidate the role of α4β1, and to identify transcription factors implicated in the regulation of α4β1 expression. We will analyze different intracellular pathways to look for altered proteins in these resistance cells.
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