Multiple Myeloma (MM) is an onco-hematologic disease characterized by high genetic heterogeneity. Evidence derived from literature has shown that MM is the consequence of a "multi-step" pathogenic process that involves several stages. During this process, the disease progressively becomes increasingly aggressive and resistant. The miRNA dysregulation, the aberrant activation of numerous signal transduction pathways (STP) and the reprogramming of common metabolic mechanisms play a key role in the MM tumorigenesis processes.
Therefore, the study of miRNA, of the aberrant STP activation profile and of the altered metabolism represent a challenge for understanding molecular determinant of resistance developed during the history of MM disease.
The aim of this project is to identify, through a combined application of innovative technologies, specific aberrant signals and peculiar metabolic phenotypes in MM cell lines and primary samples collected at diagnosis and/or at relapse/refractoriness disease.
miRNAs modulate regulatory cell pathways by influencing target genes and may serve crucial functions in oncogenesis. miRNA detection and quantification will be performed by real-time quantitative reverse-transcription polymerase-chain reaction.
Proteomic profiles of cellular populations will be analyzed by using the Reverse Phase Protein Array (RPPA), a high-throughput technology capable of processing, with high efficiency and accuracy, simultaneously numerous proteins in their total and activated form using a limited number of cells.
The impact of aberrant signal on cell metabolism will be analyzed by Seahorse XF Analyzer, a new instrument able to simultaneously measure, in real time and on live cells, several metabolic parameters and functions.
This information, along with the identification of aberrant cross-talking pathways, which may develop during the treatments history, will allow the elucidation of mechanisms involved in progression and resistance of MM.
