ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma.

Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage.

Neutralizing B-cell activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model.

Purpose: B-cell-activating factor (BAFF) is a tumor necrosis factor superfamily member critical for the maintenance and homeostasis of normal B-cell development. It has been implicated in conferring a survival advantage to B-cell malignancies, including multiple myeloma (MM).

Experimental Design: Here, we validate the role of BAFF in the in vivo pathogenesis of MM examining BAFF and its receptors in the context of patient MM cells and show activity of anti-BAFF antibody in a severe combined immunodeficient model of human MM.

Novel therapeutic approaches based on the targeting of microenvironment-derived survival pathways in human cancer: experimental models and translational issues.

It is a current idea that carcinogenesis as well as tumor progression are dynamic processes, which involve inherited as well as somatic mutations and include a continuing adaptation to different microenvironmental conditions. There is, in fact, rising evidence that tumor cells are under a persistent stress and that autocrine as well as microenvironment-derived survival factors play a substantial role for the final outcome of the tumor development as well as for response to the anti-tumor therapy. We will review current achievements on the molecular biology of the microenvironment-derived survival signaling and therapeutical approaches, which are presently under clinical development.