Role of c-MYC/miRNA-548/HDAC6 axis in drug resistance and lymphoma survival

The B cell lymphoproliferative malignancies (1) arise from B cells that require interaction with non-malignant cells and stromal cells during lymphomagenesis (2,3). There has been improvement in overall survival in these lymphomas (4), however, a significant proportion (30–40%) of cases relapse even with the introduction of rituximab in therapeutic regimens (3). Gene expression profiling studies reveal signatures originating from the microenvironment at diagnosis are significantly associated with response to therapy in follicular lymphoma (FL) and diffuse large B cell lymphomas (DLBCL) (5). Moreover, the diffuse distribution of follicular dendritic cells (FDCs) in mantle cell lymphoma (MCL) is associated with worse clinical outcome (5,6). These observations indicate that interaction between stroma and B cell lymphoma cells contributes to drug resistance and support neoplastic cell survival. A number of microRNAs (miRNAs) are dysregulated when lymphoma cells adhere to lymph node stromal cells in MCL and other B cell lymphomas (7). The dysregulated miRNAs critically influence the tumor development, progression and have been reported to be the important prognosticators in human cancers including lymphomas (8). Recently, prognostic miRNAs have identified in several NHL including DLBCL, MCL, FL and PTCL (8,9).