Assessment of MEK-ERK pathway targeting by BRAF, NRAS and KRAS gene mutations in plasma cell dyscrasias [U266 human myeloma cell line]

Multiple myeloma (MM) is a malignant disorder characterized by the clonal proliferation of plasma cells (PCs) in the bone marrow (BM). The genetic background and clinical course of the disease are largely heterogeneous, and MM pathophysiology ranges from the premalignant condition of monoclonal gammopathy of undetermined significance (MGUS) to smoldering MM, symptomatic MM, and extramedullary MM/plasma cell leukemia (PCL). Recent genome-wide sequencing efforts have provided the rationale for molecularly aimed treatment approaches, identifying mutations that can be specifically targeted, such as those in the mitogen-activated protein kinase (MAPK) pathway, which represent the most prevalent mutations in MM. Among these, mutations affecting BRAF gene, detected in 4-15% of patients, are of potential immediate clinical relevance due to the availability of effective inhibitors of this serine-threonine kinase which are in fact being explored also in myeloma.

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Lionetti M, Barbieri M, Todoerti K, Agnelli L, Marzorati S, Fabris S, Ciceri G, Galletti S, Milesi G, Manzoni M, Mazzoni M, Greco A, Tonon G, Musto P, Baldini L, Neri A