Multiple myeloma is a neoplastic plasma-cell disorder that is characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment, monoclonal protein in the blood or urine, and associated organ dysfunction.1 It accounts for approximately 1% of neoplastic diseases and 13% of hematologic cancers. In Western countries, the annual ageadjusted incidence is 5.6 cases per 100,000 persons.2 The median age at diagnosis is approximately 70 years; 37% of patients are younger than 65 years, 26% are between the ages of 65 and 74 years, and 37% are 75 years of age or older.2,3 In recent years, the introduction of autologous stem-cell transplantation and the availability of agents such as thalidomide, lenalidomide, and bortezomib have changed the management of myeloma and extended overall survival.3-5 In patients presenting at an age under 60 years, 10-year survival is approximately 30%.
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"Multiple myeloma (MM, plasma cell myeloma) is the second most prevalent B-cell cancer. Despite the availability of potent novel drugs, it remains, for the large part of patients, an incurable disease (Palumbo & Anderson, 2011; Ocio et al, 2014). MM is characterized by the expansion of malignant plasma cells predominantly within the BM. "
"MM is the second most-common hemopathy and represents 1% of all cancers. Despite the emergence of new drugs including immunomodulators (lenalinomide) and proteasome inhibitors (bortezomib) that have significantly extended patients’ survival, this disease remains incurable, with severe complications, and always leads to death . This explains the need of new drugs and/or therapeutic strategies. "
[Show abstract][Hide abstract]ABSTRACT: Tumoral plasma cells has retained stemness features and in particular, a polycomb-silenced gene expression signature. Therefore, epigenetic therapy could be a mean to fight for multiple myeloma (MM), still an incurable pathology. Deazaneplanocin A (DZNep), a S-adenosyl-L-homocysteine hydrolase inhibitor, targets enhancer of zest homolog 2 (EZH2), a component of polycomb repressive complex 2 (PRC2) and is capable to induce the death of cancer cells. We show here that, in some MM cell lines, DZNep induced both caspase-dependent and -independent apoptosis. However, the induction of cell death was not mediated through its effect on EZH2 and the trimethylation on lysine 27 of histone H3 (H3K27me3). DZNep likely acted through non-epigenetic mechanisms in myeloma cells. In vivo, in xenograft models, and in vitro DZNep showed potent antimyeloma activity alone or in combination with bortezomib. These preclinical data let us to envisage new therapeutic strategies for myeloma.
"These strategies have improved overall survival of MM patients. However, most patients eventually relapse even after the achievement of complete response . Therefore, other novel therapeutic approaches are strongly needed to further improve the outcome of MM. "
[Show abstract][Hide abstract]ABSTRACT: Multiple myeloma (MM) still remains an incurable disease, at least because of the existence of cell-adhesion mediated drug-resistant MM cells and/or continuous recruitment of presumed MM cancer stem cell-like cells (CSCs). As a new alternative treatment modality, immunological approaches using monoclonal antibodies (mAbs) and/or cytotoxic T lymphocytes (CTLs) are now attracting much attention as a novel strategy attacking MM cells. We have identified that HM1.24 [also known as bone marrow stromal cell antigen 2 (BST2) or CD317] is overexpressed on not only mature MM cells but also MM CSCs. We then have developed a humanized mAb to HM1.24 and defucosylated version of the mAb to adapt to clinical practice. Moreover, we have successfully induced HM1.24-specific CTLs against MM cells. The combination of these innovative therapeutic modalities may likely exert an anti-MM activity by evading the drug resistance mechanism and eliminating presumed CSCs in MM.
Full-text · Article · Jul 2014 · BioMed Research International