Clinical implication of centrosome amplification in plasma cell neoplasm

The mechanisms underlying aneuploidy in multiple myeloma (MM) are unclear. Centrosome amplification has been implicated as the cause of chromosomal instability in a variety of tumors and is a potential mechanism causing aneuploidy in MM. Using immunofluorescent (IF) staining, centrosome amplification was detected in 67% of monoclonal gammopathies, including monoclonal gammopathy of undetermined significance (MGUS). We also investigated the gene expression of centrosome proteins. Overall, gene expression data correlated well with IF-detected centrosome amplification, allowing us to derive a gene expression-based centrosome index (CI) as a surrogate for centrosome amplification. Clinically, MM patients with high CI (> 4) are associated with poor prognostic genetic and clinical subtypes (chromosome 13 deletion, t(4; 14), t(14;16), and PCLI > 1%, P < .05) and are shown here to have short survival (11.1 months versus 39.1 months, P < .001). On multivariate regression, a high CI is an independent prognostic factor. Given that centrosome amplification is already observed in MGUS and probably integral to early chromosomal instability and myeloma genesis, and patients with more extensive centrosome amplification have shorter survival, the mechanisms leading to centrosome amplification should be investigated because these may offer new avenues for therapeutic intervention.

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Microarray Demonstrates Different Gene Expression Profiling Signatures Between Waldenström Macroglobulinemia and IgM Monoclonal Gammopathy of Undetermined Significance

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2013.02.012 ◽

2013 ◽

Vol 13 (2) ◽

pp. 208-210 ◽

Cited By ~ 5

Author(s):

Alessandra Trojani ◽

Antonino Greco ◽

Alessandra Tedeschi ◽

Milena Lodola ◽

Barbara Di Camillo ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Monoclonal Gammopathy ◽

Waldenström Macroglobulinemia ◽

Waldenstrom Macroglobulinemia ◽

Undetermined Significance

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Thymic plasma cell neoplasm infiltration in Sjögren’s syndrome with monoclonal gammopathy

Rheumatology ◽

10.1093/rheumatology/key074 ◽

2018 ◽

Vol 57 (8) ◽

pp. 1416-1416

Author(s):

Yoshinori Taniguchi ◽

Satoshi Inotani ◽

Yoshio Terada

Keyword(s):

Sjögren’S Syndrome ◽

Plasma Cell ◽

Monoclonal Gammopathy ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Plasma Cell Neoplasm ◽

Cell Neoplasm ◽

Sjögren‘S Syndrome

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PSMB7 Is a Key Gene Involved in the Development of Multiple Myeloma and Resistance to Bortezomib

Frontiers in Oncology ◽

10.3389/fonc.2021.684232 ◽

2021 ◽

Vol 11 ◽

Author(s):

Dong Wu ◽

Jiyu Miao ◽

Jinsong Hu ◽

Fangmei Li ◽

Dandan Gao ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Drug Resistance ◽

Treatment Group ◽

Monoclonal Gammopathy ◽

Plasma Cells ◽

Proteasome Inhibitors ◽

Hematologic Neoplasm ◽

Almost All ◽

Undetermined Significance

Multiple myeloma (MM), the second most commonly diagnosed hematologic neoplasm, is the most significant clinical manifestation in a series of plasma cell (PC) dyscrasia. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM), approximately 1% or 10% of which, respectively, can progress to MM per year, are the premalignant stages of MM. The overall survival (OS) of MM is significantly improved by the introduction of proteasome inhibitors (PIs), but almost all MM patients eventually relapse and resist anti-MM drugs. Therefore, it is crucial to explore the progression of MM and the mechanisms related to MM drug resistance. In this study, we used weighted gene co-expression network analysis (WGCNA) to analyze the gene expression of the dynamic process from normal plasma cells (NPC) to malignant profiling PC, and found that the abnormal gene expression was mainly concentrated in the proteasome. We also found that the expression of one of the proteasomal subunits PSMB7 was capable of distinguishing the different stages of PC dyscrasia and was the highest in ISS III. In the bortezomib (BTZ) treated NDMM patients, higher PSMB7 expression was associated with shorter survival time, and the expression of PSMB7 in the BTZ treatment group was significantly higher than in the thalidomide (Thai) treatment group. In summary, we found that PSMB7 is the key gene associated with MM disease progression and drug resistance.

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Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells

Blood ◽

10.1182/blood.v99.5.1745 ◽

2002 ◽

Vol 99 (5) ◽

pp. 1745-1757 ◽

Cited By ~ 455

Author(s):

Fenghuang Zhan ◽

Johanna Hardin ◽

Bob Kordsmeier ◽

Klaus Bumm ◽

Mingzhong Zheng ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Multiple Myeloma ◽

Bone Marrow ◽

Expression Profiling ◽

Monoclonal Gammopathy ◽

Plasma Cells ◽

Disease Genes ◽

Bone Marrow Plasma ◽

Undetermined Significance

Bone marrow plasma cells (PCs) from 74 patients with newly diagnosed multiple myeloma (MM), 5 with monoclonal gammopathy of undetermined significance (MGUS), and 31 healthy volunteers (normal PCs) were purified by CD138+ selection. Gene expression of purified PCs and 7 MM cell lines were profiled using high-density oligonucleotide microarrays interrogating about 6800 genes. On hierarchical clustering analysis, normal and MM PCs were differentiated and 4 distinct subgroups of MM (MM1, MM2, MM3, and MM4) were identified. The expression pattern of MM1 was similar to normal PCs and MGUS, whereas MM4 was similar to MM cell lines. Clinical parameters linked to poor prognosis, abnormal karyotype (P = .002) and high serum β2-microglobulin levels (P = .0005), were most prevalent in MM4. Also, genes involved in DNA metabolism and cell cycle control were overexpressed in a comparison of MM1 and MM4. In addition, using χ2 and Wilcoxon rank sum tests, 120 novel candidate disease genes were identified that discriminate normal and malignant PCs (P < .0001); many are involved in adhesion, apoptosis, cell cycle, drug resistance, growth arrest, oncogenesis, signaling, and transcription. A total of 156 genes, including FGFR3 andCCND1, exhibited highly elevated (“spiked”) expression in at least 4 of the 74 MM cases (range, 4-25 spikes). Elevated expression of these 2 genes was caused by the translocation t(4;14)(p16;q32) or t(11;14)(q13;q32). Thus, novel candidate MM disease genes have been identified using gene expression profiling and this profiling has led to the development of a gene-based classification system for MM.

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