[POEMS syndrome: advances in molecular pathophysiology and treatment].

ABSTRACT

POEMS syndrome is a rare paraneoplastic disorder characterized by polyneuropathy, organomegaly, endocrinopathy, λ-type monoclonal protein derived from only two germlines (IGLV1-40 or IGLV1-44), skin changes, extravascular volume overload, and serum vascular endothelial growth factor elevation. To understand the molecular pathophysiology of the disease, comprehensive genetic analyses of bone marrow plasma cells was performed in 20 patients with the syndrome. Although a median of 14.5 mutated genes were identified per patient, none of the driver gene mutations frequently found in multiple myeloma were detected. RNA sequencing revealed a transcription profile specific to POEMS syndrome, which suggested that the genetic and transcriptional profiles of plasma cells in POEMS syndrome are distinct from multiple myeloma and monoclonal gammopathy of undetermined significance. Treatment strategies for the devastating disease have been developed by targeting monoclonal plasma cells with novel agents, mainly thalidomide, followed by autologous stem cell transplantation (ASCT). Moreover, the 5-year overall survival after ASCT has improved to as high as 90% with dramatic improvement in symptoms and activities of daily living. However, the 5-year progression-free survival during long-term follow-up has dropped to 60%. Therefore, identifying novel therapeutic targets are imperative for further improvement of disease outcomes.