RESUMO
Background: The nonrandom recurrence of chromosomal abnormalities in multiple myeloma (MM) raises the possibility that they play a role in the pathophysiology and development of the disease. Fluorescence in situ hybridization (FISH) can identify a high frequency of certain abnormalities without the need for the proliferative and infiltrative index of malignant plasma cells required for conventional cytogenetic analysis. In this study, we describe the association between clinico-biological characteristics and chromosomal abnormalities in 30 Moroccan patients. Methods: The analysis of cytogenetic data, conventional and molecular, of 30 cases of MM, obtained from our previously cytogenetic study, and correlation of the results with the clinico-biological data of these patients. Results: The bone marrow of 5 of 21 patients (23 %) contained a chromosomally abnormal clone, and all karyotypes were complicated (>3 abnormalities). Interphase FISH (iFISH) has detected aberrations in 14 out of 30 (46 %) of the total cases. The proportion of plasma cells in the bone marrow was higher in patients with chromosomal abnormalities (median 29 %) (p = 0.01917) than in patients without abnormalities (median 11 %). Although there was a difference in the median ß-2 microglobulin percentage (13.8 % versus 6.8 %), it was not statistically significant (p = 0.6818). We also, categorized patients into those with a complex clone and those with a sole abnormality. Patients with high bone marrow plasma cell rate (median 45 %) and high rate of ß-2 microglobulin (median 24 %) showed a complex karyotype and a higher iFISH detection rate than those with plasma cells count for (median 20 %) and ß-2 microglobulin count for (median 11 %) but without statistical significance (p = 0.4338 et p = 0.45 respectively). Furthermore, patients with aberrations had significantly shorter overall survival (100 % for 800 days versus 150 days only). Conclusion: Our research has shown that different subgroups of patients with MM can be classified based on the underlying genetic abnormalities. Chromosomal abnormalities (CA) may give the plasma cell a proliferative advantage, increasing the virulence of the disease and affecting overall survival.
RESUMO
Multiple myeloma (MM) is a hematological malignancy in which monoclonal plasma cells multiply in the bone marrow and monoclonal immunoglobulins are overproduced in older people. Several molecular and cytogenetic advances allow scientists to identify several genetic and chromosomal abnormalities that cause the disease. The comprehension of the pathophysiology of MM requires an understanding of the characteristics of malignant clones and the changes in the bone marrow microenvironment. This study aims to identify the central genes and to determine the key signaling pathways in MM by in silico approaches. A list of 114 differentially expressed genes (DEGs) is important in the prognosis of MM. The DEGs are collected from scientific publications and databases (https://www.ncbi.nlm.nih.gov/). These data are analyzed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software (https://string-db.org/) through the construction of protein-protein interaction (PPI) networks and enrichment analysis of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, by CytoHubba, AutoAnnotate, Bingo Apps plugins in Cytoscape software (https://cytoscape.org/) and by DAVID database (https://david.ncifcrf.gov/). The analysis of the results shows that there are 7 core genes, including TP53; MYC; CDND1; IL6; UBA52; EZH2, and MDM2. These top genes appear to play a role in the promotion and progression of MM. According to functional enrichment analysis, these genes are mainly involved in the following signaling pathways: Epstein-Barr virus infection, microRNA pathway, PI3K-Akt signaling pathway, and p53 signaling pathway. Several crucial genes, including TP53, MYC, CDND1, IL6, UBA52, EZH2, and MDM2, are significantly correlated with MM, which may exert their role in the onset and evolution of MM.
