Multiple Myeloma

Myeloma Unit, Division of Hematology, University of Turin, AOU S. Giovanni Battista, Turin, Italy.
New England Journal of Medicine (Impact Factor: 55.87). 03/2011; 364(11):1046-60. DOI: 10.1056/NEJMra1011442
Source: PubMed


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. "
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    ABSTRACT: CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination and poor prognosis. We evaluated the novel CXCR4 probe [(68)Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [(68)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [(68)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [(18)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34(+) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [(68)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
    EMBO Molecular Medicine 02/2015; 7(4). DOI:10.15252/emmm.201404698 · 8.67 Impact Factor
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    • "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 [1]. This explains the need of new drugs and/or therapeutic strategies. "
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    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.
    PLoS ONE 09/2014; 9(9):e107009. DOI:10.1371/journal.pone.0107009 · 3.23 Impact Factor
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    • "These strategies have improved overall survival of MM patients. However, most patients eventually relapse even after the achievement of complete response [4]. Therefore, other novel therapeutic approaches are strongly needed to further improve the outcome of MM. "
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    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.
    BioMed Research International 07/2014; 2014:965384. DOI:10.1155/2014/965384 · 3.17 Impact Factor
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