Centrosome amplification as a possible marker of mitotic disruptions and cellular carcinogenesis in multiple myeloma

Dementyeva, Elena Vladimirovna; Němec, Pavel; Kryukov, Fedor; Raja, Karthick Raja Muthu; Smetana, Jan; Zaoralová, Romana; Grešlíková, Henrieta; Kupská, Renata; Kuglík, Petr

doi:10.1016/j.leukres.2009.12.018

Cited by 12 publications

(12 citation statements)

References 25 publications

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“…1B), which agrees with the finding by Dementyeva and do-workers that approximately 3% of the peripheral blood cells from healthy donors display centrosome amplification [28]. …”

Section: Discussionsupporting

confidence: 91%

Type 2 Diabetes Promotes Cell Centrosome Amplification via AKT-ROS-Dependent Signalling of ROCK1 and 14-3-3σ

Wang¹,

Lü²,

Wang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Type 2 diabetes is associated with oxidative stress and DNA damage which can cause centrosome amplification. Thus, the study investigated centrosome amplification in type 2 diabetes and the underlying mechanisms. Methods: Centrosome numbers in human peripheral blood mononuclear blood cells (PBMC) from healthy subjects and patients with type 2 diabetes were compared to access the association between type 2 diabetes and centrosome amplification. Colon cancer cells were used to investigate the molecular mechanisms underlying the centrosome amplification triggered by high glucose, insulin and palmitic acid. Western blot analysis was used to quantify the level of protein and protein phosphorylation. Immunofluorescent staining was performed to detect centrosomes. ROS was quantified using flow cytometry technique. Transcriptpmic profiling was performed using Illumina HiSeq^TM500 platform. Results: We found that centrosome amplification was increased PBMC from the type 2 diabetic patients, which correlated with the levels of fasting blood glucose and HbA1c. High glucose, insulin and palmitic acid, alone or in combinations, induced ROS production and centrosome amplification. Together, they increased AKT activation as well as the expression, binding and centrosome translation of ROCK1 and 14-3-3σ. Results from further analyses showed that AKT-ROS-dependent upregulations of expression, binding and centrosome translocation of ROCK1 and 14-3-3σ was the molecular pathway underlying the centrosome amplification in vitro triggered by high glucose, insulin and palmitic acid. Moreover, the key in vitro molecular signalling events activated by high glucose, insulin and palmitic acid were verified in PBMC from the patients with type 2 diabetes. Conclusion: Our results show that type 2 diabetes promotes cell centrosome amplification, and suggest that the diabetic pathophysiological factors-activated AKT-ROS-dependent signalling of ROCK1 and 14-3-3σ is the underlying molecular mechanism.

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“…1B), which agrees with the finding by Dementyeva and do-workers that approximately 3% of the peripheral blood cells from healthy donors display centrosome amplification [28]. …”

Section: Discussionsupporting

confidence: 91%

Type 2 Diabetes Promotes Cell Centrosome Amplification via AKT-ROS-Dependent Signalling of ROCK1 and 14-3-3σ

Wang¹,

Lü²,

Wang³

et al. 2018

Cell Physiol Biochem

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“…Interestingly, no difference in CA exists between ploidy categories in myeloma, suggesting that CA contributes to genomic instability in both tumour subgroups. Expanding upon these observations, CA is also evident in B-cells of MM patients, supporting the existence of an abnormal clonal population of B-cells which may be precursors of malignant plasma cells 198.…”

Section: Centrosome Amplification In Haematological Malignanciesmentioning

confidence: 60%

A Clinical Overview of Centrosome Amplification in Human Cancers

Chan¹

2011

Int. J. Biol. Sci.

335

349

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The turn of the 21st century had witnessed a surge of interest in the centrosome and its causal relation to human cancer development - a postulate that has existed for almost a century. Centrosome amplification (CA) is frequently detected in a growing list of human cancers, both solid and haematological, and is a candidate "hallmark" of cancer cells. Several lines of evidence support the progressive involvement of CA in the transition from early to advanced stages of carcinogenesis, being also found in pre-neoplastic lesions and even in histopathologically-normal tissue. CA constitutes the major mechanism leading to chromosomal instability and aneuploidy, via the formation of multipolar spindles and chromosomal missegregation. Clinically, CA may translate to a greater risk for initiation of malignant transformation, tumour progression, chemoresistance and ultimately, poor patient prognosis. As mechanisms underlying CA are progressively being unravelled, the centrosome has emerged as a novel candidate target for cancer treatment. This Review summarizes mainly the clinical studies performed to date focusing on the mechanisms underlying CA in human neoplasia, and highlights the potential utility of centrosomes in the diagnosis, prognosis and treatment of human cancers.

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“…PCs visualization with immunoglobulin light chain staining (cIg) and immunofluorescent labeling of centrin as an integral centrosome protein for centrosome copy number determination, was performed as described previously [32,34]. Brief workflow was as follows:…”

Section: Design and Methodsmentioning

confidence: 99%

“…Up to four centrin signals (representing four centrioles of two centrosomes) can be present in a normal cell depending on the phase of cell cycle. Samples with more than 10% of PCs with >4 signals of centrin were considered as CA-positive (Figure 1) [31,32,34]. …”

Section: Design and Methodsmentioning

confidence: 99%

“…Malignant PCs have a proliferation rate that increases from the early to the advanced stage of plasma cell dyscrasia [23-25] and this proliferative feature is one of the strongest adverse prognostic factors [25-29]. High proliferation myeloma cell index estimates range from 1 to 3% [26,30], but approximately one third of PCs contain centrosome amplification (CA) [31,32]. It appears to be plausible that deregulation of the cell cycle earlier during MM pathogenesis leads to accumulation of centrosomes and their succession to aberrant PC.…”

Section: Introductionmentioning

confidence: 99%

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Clinical implication of centrosome amplification and expression of centrosomal functional genes in multiple myeloma

et al. 2013

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BackgroundMultiple myeloma (MM) is a low proliferative tumor of postgerminal center plasma cell (PC). Centrosome amplification (CA) is supposed to be one of the mechanisms leading to chromosomal instability. Also, CA is associated with deregulation of cell cycle, mitosis, DNA repair and proliferation. The aim of our study was to evaluate the prognostic significance and possible role of CA in pathogenesis and analysis of mitotic genes as mitotic disruption markers.Design and methodsA total of 173 patients were evaluated for this study. CD138+ cells were separated by MACS. Immunofluorescent labeling of centrin was used for evaluation of centrosome amplification in PCs. Interphase FISH with cytoplasmic immunoglobulin light chain staining (cIg FISH) and qRT-PCR were performed on PCs.ResultsBased on the immunofluorescent staining results, all patients were divided into two groups: CA positive (38.2%) and CA negative (61.8%). Among the newly diagnosed patients, worse overall survival was indicated in the CA negative group (44/74) in comparison to the CA positive group (30/74) (P = 0.019).Gene expression was significantly down-regulated in the CA positive group in comparison to CA negative in the following genes: AURKB, PLK4, TUBG1 (P < 0.05). Gene expression was significantly down-regulated in newly diagnosed in comparison to relapsed patients in the following genes: AURKA, AURKB, CCNB1, CCNB2, CETN2, HMMR, PLK4, PCNT, and TACC3 (P < 0.05).ConclusionsOur findings indicate better prognosis for CA positive newly diagnosed patients. Considering revealed clinical and gene expression heterogeneity between CA negative and CA positive patients, there is a possibility to characterize centrosome amplification as a notable event in multiple myeloma pathogenesis.

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Centrosome amplification as a possible marker of mitotic disruptions and cellular carcinogenesis in multiple myeloma

Cited by 12 publications

References 25 publications

Type 2 Diabetes Promotes Cell Centrosome Amplification via AKT-ROS-Dependent Signalling of ROCK1 and 14-3-3σ

Type 2 Diabetes Promotes Cell Centrosome Amplification via AKT-ROS-Dependent Signalling of ROCK1 and 14-3-3σ

A Clinical Overview of Centrosome Amplification in Human Cancers

Clinical implication of centrosome amplification and expression of centrosomal functional genes in multiple myeloma

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