Expression of MCL1, GSTP1 and CKS1B genes in patients with monoclonal gammopathy of undetermined significance and multiple myeloma

FLAVIA STELLA; DOROTEA BEATRIZ FANTL; JORGE ARBELBIDE; NATALIA SCHUTZ; IRMA SLAVUTSKY

Amsterdam

Congreso; 17th Congress of the European Hematology Association; 2012

European Hematology Association

Background: Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) comprise heterogeneous disorders with incompletely understood molecular defects and variable clinical features. Molecular studies have identified genes differentially expressed in MM but some of them have been scarcely explored in MGUS patients. Aim: The aim of this study was to evaluate mRNA expression of MCL1, GSTP1 and CKS1B genes in patient with MGUS and MM in order to analyze their participation in the progression of disease. Methods: Bone marrow samples from 90 patients: 60 with MM (26 males; mean age: 66.4 years; range: 30-86 years; Durie & Salmon stage: I: 21%, II: 17%, III: 62%) and 30 with MGUS (9 males; mean age: 70.6 years; range: 41-84 years) and, mononuclear cells from 11 normal controls, were analyzed. Patients were studied at diagnosis. All individuals gave informed consent and the study was approved by the local Ethics Committee. Real-Time Quantitative PCR was used to quantify gene expression. For statistical analysis, Mann-Whitney test and Kendal coefficient were used. Results: Analysis of mRNA expression showed differences among evaluated genes. MCL1 had overexpression only in MM patients (24.69±11.05) with significant differences with respect to controls (4.13±1.14) (p<0.0001). GSTP1 and CKS1B genes showed abnormal expression in both MM and MGUS patients. Overexpression of GSTP1 gene was observed in 32% of MM and 33% of MGUS patients. Although MGUS mRNA levels (0.05±0.01) were lower than those of MM patients (0.12±0.05), no significant differences between them were observed. The analysis of CKS1B also showed abnormal expression in a similar percentage of MM and MGUS patients (60% and 50%, respectively). Comparison of mRNA values showed higher CKS1B expression in MM (0.017±0.006) with respect to MGUS patients (0.004±0.001) (p<0.04) and in both entities compared to controls (0.002±0.0004) (p<0.04). The analysis of clinical characteristics in MM patients showed a positive association between â2microglobuline and MCL1 mRNA levels (p=0.015). Expression of CKS1B was positively correlated with the percentage of bone marrow infiltration (p=0.0012; r2=0.1942) and M protein levels (p=0.0005; r2=0.2415). GSTP1 gene expression did not show association with clinical parameters. Conclusions: To our knowledge, this is the first evaluation of GSTP1 mRNA expression in MGUS patients. Our data showed deregulation of GSTP1 and CKS1B genes in this disorder. Significant differences in CKS1B expression between MM and MGUS and a positive association with bone marrow infiltration suggest a role for this gene in the progression from MGUS to MM.