Introduction. In recent years global gene expression profiling studies introduce several new potential prognostic markers in multiple myeloma (MM). Up-regulation and amplification of the gene CKS1B in myeloma cells has lately been associated with a poor prognosis in MM patients. The CKS1B gene is located on chromosome 1q and is involved in the induction of cell proliferation by inhibiting the cyclin-dependent kinase inhibitor p27(kip1). Materials and Methods. We investigated the prognostic value of CKS1B expression by real time quantitative polymerase chain reaction techniques in purified myeloma cells from 171 untreated, newly diagnosed MM-patients. 36% of the patients (<65 years) were treated with high dose melphalan (200 mg/m2) with stem cell support. 56% (>65 years) were treated with standard melphalan and prednisolone, and 8% were untreated. Median follow-up was 53 months. The clonal myeloma cells in bone marrow aspirates were immunophenotyped by 3- og 4-colour flowcytometry, and patients were only included if an aberrant clone was identified. Herafter, aberrant plasma cells (CD38++/CD19-/CD45-/i/CD56-/+/++) were sorted directly into PCR tubes by fluorescence activated cell sorting (FACS) using af FACS Aria (BDIS). In all cases plasma cell purity above 98% was obtained. Purified normal plasma cells from 9 healthy volunteers were collected as controls. A cDNA archive was generated by global reverse transcription. By using a polyadenylating step 5/-oligo(dT)-transcript-poly(A)-3/cDNA were generated and finally amplified by PCR using a sequence independent X-(dT)24 primer. Gene expression of CSK1B and the housekeeping gene ß-actin were analysed by RQ-PCR and CKS1B expression levels were normalized to ß-actin. Expression of CKS1B was observed in 52% of the patients. Results and Conclusions. We investigated the prognostic value of CKS1B expression by quantitative PCR techniques in, flowcytometry sorted, highly purified myeloma cells from 171 untreated MM patients. CKS1B over-expression did not correlate with af poor outcome in the patients. In the high dose melphalan treated patients the overall survival was similar in patients with or without up-reulated CKS1B expression. In patients treated with conventional chemotherapy expression of CKS1B showed a trend towards a survival benefit (p=0.05). So, our data do not confirm that myeloma celle over-expression of CKS1B is associated with af poor prognosis.
|Status||Udgivet - 2007|
|Begivenhed||XIth International Myeloma WorkshopIVth International Workshop on Waldenström's Macroglobulinemia - Kos Island, Grækenland|
Varighed: 25. jun. 2007 → 30. jun. 2007
Konferencens nummer: XI
|Konference||XIth International Myeloma WorkshopIVth International Workshop on Waldenström's Macroglobulinemia|
|Periode||25/06/2007 → 30/06/2007|