RESUMEN
Although multiple myeloma (MM) is a neoplasm that leads affected individuals to death, little is known about why some patients survive much longer than others. In this context, we investigated the transcriptomic profile of bone marrow hematopoietic stem cells obtained from MM patients and compared the clinical outcomes of death and survival six months after bone marrow transplantation. The leukapheresis products of 39 patients with MM eligible for autologous transplantation were collected and analyzed. After extraction, the RNA was analyzed using the GeneChip Human Exon 1.0 Array method. The transcriptome profile was analyzed in silico, and the differentially expressed signaling pathways of interest were validated. The results showed a difference in the expression of inflammation-related genes, immune response processes, and the oxidative stress pathway. The in silico study also pointed out the involvement of the NFκB transcription factor in the possible modulation of these genes. We chose to validate molecules participating in these processes, including the cytokines TNF-α, IFN-γ, and TGF-ß1; in addition, we measured the levels of oxidative stress mediators (pro-oxidant profile and the total antioxidant capacity). TNF-α levels were significantly reduced in patients who died and were over 50 years old at diagnosis, as well as in patients with plasmacytoma. Increased TNF-α was detected in patients with very high levels of ß2-microglobulin. IFN-γ reduction was observed in patients with a complete response to treatment compared to those with a very good response. Patients with plasmacytoma who died also had an increased pro-oxidant profile. These data show the profile of inflammatory response markers that are altered in patients with MM who die quickly and serve as a basis for the development of future studies of markers to predict better survival in this disease.
