Publications

Molecular analysis of RAS-RAF tyrosine-kinase signaling pathway alterations in patients with plasma cell myeloma

Grossmann, V., Bacher, U., Artusi, V., Kohlmann, A., Nadarajah, N., Kern, W., Schnittger, S., Haferlach, T., Haferlach, C.

In patients with plasma cell myeloma (PCM), interphase fluorescence in situ hybridization (FISH) detects prognostically relevant genetic alterations, for example, the prognostically adverse t(4;14)(p16;q32) or 17p deletions. Furthermore, mutations of the RAS protooncogene were suggested to be associated to myeloma pathogenesis. The RAS pathway inhibitor lonafarnib combined with the proteasome inhibitor bortezomib demonstrated synergistic cell death in human myeloma cells in association with downregulation of p-AKT in an in vitro setting. By whole-genome and whole-exome sequencing, Chapman et al. found frequent involvement of genes associated to the nuclear factor-kappaB pathway. Rare PCM cases were positive for BRAF mutations,3 which had previously been detected in solid tumors (for example, melanoma) and hematological neoplasms, for example, hairy cell leukemia.

Citation

Grossmann, V., Bacher, U., Artusi, V., Kohlmann, A., Nadarajah, N., Kern, W., Schnittger, S., Haferlach, T., Haferlach, C. "Molecular analysis of RAS-RAF tyrosine-kinase signaling pathway alterations in patients with plasma cell myeloma" Blood Cancer Journal (2012): e85