HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Expression of eight genes of nuclear factor-kappa B pathway in multiple myeloma using bone marrow aspirates obtained at diagnosis

Manuella S. Sampaio Almeida1, André L. Vettore2,4, Mihoko Yamamoto1, Maria de Lourdes L.F. Chauffaille1, Marco Antônio Zago3 and Gisele W. B. Colleoni1

1Department of Hematology and Hemotherapy, Universidade Federal de São Paulo, UNIFESP/EPM, São Paulo, Brazil, 2Ludwig Institute for Cancer Research, São Paulo Branch, Brazil, 3Faculdade de Medicina de Ribeirão Preto/USP, Brazil and 4Biology Department, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil.

Offprint requests to: Giselle Colleoni, Disciplina de Hematologia e Hemoterapia, UNIFESP, Rua Botucatu, 740, 3º andar, Via Clementino, Cep: 04023-900, Sao Paulo, SP, Brasil. e-mail: gcolleoni@hemato.epm.br


Summary. Purpose: To evaluate the expression of NF-κB pathway genes in total bone marrow samples obtained from MM at diagnosis using real-time quantitative PCR and to evaluate its possible correlation with disease clinical features and survival. Material and methods: Expression of eight genes related to NF-
κB pathway (NFKB1, IKB, RANK, RANKL, OPG, IL6, VCAM1 and ICAM1) were studied in 53 bone marrow samples from newly diagnosed MM patients and in seven normal controls, using the Taqman system. Genes were considered overexpressed when tumor expression level was at least four times higher than that observed in normal samples. Results: The percentages of overexpression of the eight genes were: NFKB1 0%, IKB 22.6%, RANK 15.1%, RANKL 31.3%, OPG 7.5%, IL6 39.6%, VCAM1 10% and ICAM1 26%. We found association between IL6 expression level and International Staging System (ISS) (p=0.01), meaning that MM patients with high ISS scores have more chance of overexpression of IL6. The mean value of ICAM1 relative expression was also associated with the ISS score (p=0.02). Regarding OS, cases with IL6 overexpression present worse evolution than cases with IL6 normal expression (p=0.04). Conclusion: We demonstrated that total bone marrow aspirates can be used as a source of material for gene expression studies in MM. In this context, we confirmed that IL6 overexpression was significantly associated with worse survival and we described that it is associated with high ISS scores. Also, ICAM1 was overexpressed in 26% of cases and its level was associated with ISS scores. Histol Histopathol 24, 991-997 (2009)

Key words: Multiple myeloma, International staging System, Nuclear factor-kappa B, Interleukin-6, Prognosis

DOI: 10.14670/HH-24.991