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

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DEMENTYEVA Elena KRYUKOV Fedor KUBICZKOVÁ Lenka NĚMEC Pavel ŠEVČÍKOVÁ Sabina IHNATOVÁ Ivana JARKOVSKÝ Jiří MINARIK Jiri STEFANIKOVA Zdena KUGLÍK Petr HÁJEK Roman

Rok publikování 2013
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Translational Medicine
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Doi http://dx.doi.org/10.1186/1479-5876-11-77
Obor Fyziologie
Klíčová slova Multiple myeloma; Centrosome amplification; Overall survival
Přiložené soubory
Popis Background: Multiple 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 methods: A 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. Results: Based 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). Conclusions: Our 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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