Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSC) are contributing to an immunosuppressive environment by their ability to inhibit T cell activity and thereby promoting cancer progression. An important feature of the incurable plasma cell malignancy Multiple Myeloma (MM) is immune dysfunction. MDSC were previously identified to be present and active in MM patients, however little is known about the MDSC-inducing and -activating capacity of MM cells.

Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells.

The interplay between bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells performs a crucial role in MM pathogenesis by secreting growth factors, cytokines, and extracellular vesicles. Exosomes are membranous vesicles 40 to 100 nm in diameter constitutively released by almost all cell types, and they mediate local cell-to-cell communication by transferring mRNAs, miRNAs, and proteins. Although BMSC-induced growth and drug resistance of MM cells has been studied, the role of BMSC-derived exosomes in this action remains unclear.

The role of DNA damage and repair in decitabine-mediated apoptosis in multiple myeloma.

DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) are under investigation for the treatment of cancer, including the plasma cell malignancy multiple myeloma (MM). Evidence exists that DNA damage and repair contribute to the cytotoxicity mediated by the DNMTi decitabine. Here, we investigated the DNA damage response (DDR) induced by decitabine in MM using 4 human MM cell lines and the murine 5T33MM model.

The HDAC inhibitor LBH589 enhances the antimyeloma effects of the IGF-1RTK inhibitor picropodophyllin.

Purpose: We have previously shown the use of the insulin-like growth factor type 1 receptor tyrosine kinase (IGF-1RTK) inhibitor picropodophyllin (PPP) as an attractive strategy to combat multiple myeloma (MM) in vitro and in vivo. After a combinatorial drug screening, the histone deacetylase inhibitor LBH589 was shown to act in synergy with PPP reducing survival of MM cells. In this study, we tried to elucidate the molecular mechanisms underlying this combinatorial effect.

The microenvironment and molecular biology of the multiple myeloma tumor.

Multiple myeloma (MM) is a deadly plasma cell cancer that resides in the bone marrow (BM). Numerous studies have demonstrated the involvement of the BM microenvironment supporting tumor growth, angiogenesis, bone disease and drug resistance. Reciprocal interactions between the different components of the BM microenvironment and the MM cells are necessary to regulate migration, differentiation, proliferation and survival of the malignant plasma cells.

Polycomb target genes are silenced in multiple myeloma.

Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpressed gene signature in MM patient cells compared to normal counterpart plasma cells.

Bortezomib alone or in combination with the histone deacetylase inhibitor JNJ-26481585: effect on myeloma bone disease in the 5T2MM murine model of myeloma.

The proteasome inhibitor bortezomib (Velcade) is currently approved as second-line treatment of multiple myeloma (MM). MM-related bone disease is one of the most debilitating complications of MM. Besides supportive care with biphosphonates, which have proven efficacy in reducing and delaying skeletal-related events, there is no specific treatment of lytic bone lesions.