Abstract
Multiple myeloma (MM) is characterized by malignant proliferation of plasma cells (PC) which accumulate in the bone marrow (BM). The advent of new drugs has changed the course of the disease from incurable to treatable, but most patients eventually relapse. One group of MM patients (10-15%) is considered high-risk because they relapse within 24 months. Recently, extramedullary relapse of MM (EM) has been observed more frequently. Due to its aggressivity and shorter survival, EM is also considered high-risk. The goal of this study was to determine if the so-called high-risk genes published by the University of Arkansas group (UAMS) are even more deregulated in EM patients than in high-risk MM patients and if these patients may be considered high-risk. Nine samples of bone marrow plasma cells from MM patients as well as 9 tumors and 9 bone marrow plasma cells from EM patients were used. Quantitative real-time PCR was used for evaluation of expression of 15 genes connected to the high-risk signature of MM patients. Comparison of high-risk plasma cells vs extramedullary plasma cells revealed 4 significantly deregulated genes (CKS1B, CTBS, NADK, YWHAZ); moreover, comparison of extramedullary plasma cells vs extramedullary tumors revealed significant differences in 9 out of 15 genes. Of these, 6 showed significant changes as described by the UAMS group (ASPM, SLC19A1, NADK, TBRG4, TMPO and LARS2). Our data suggest that increasing genetic abnormalities as described by the gene expression data are associated with increased risk for EM relapse.
Highlights
Multiple myeloma (MM) is the second most common hematological malignancy in the world. It is characterized by malignant proliferation of a clone of plasma cells (PC) that produce a specific type of monoclonal immunoglobulin
Significant differences were established among three groups of patients – high-risk MM (HR PC) versus extramedullary relapse of MM (EM) (EM PC) (Table 3a), HR PC versus EM tumor (EM T) (Table 3b) and EM PC versus EM T (Table 3c)
The third comparison of gene expression between EM PC and EM T groups revealed the greatest proportion of statistically significant differences in 9 out of 15 genes
Summary
Multiple myeloma (MM) is the second most common hematological malignancy in the world. Based on the newest guidelines of the International Myeloma Working Group (IMWG) published in 2014, high-risk MM is defined by ISS stage II or III, the presence of either t(4,14) or del17p13 and comprises about 20% of patients[4] These patients relapse early, their remissions are of short duration and the disease eventually becomes refractory. High-risk patients show high levels of beta-2 microglobulin and creatinine, deletion of chromosome 13 and other abnormalities with negative influence on patient survival This GEP model was later simplified to 17 gene expression out of the original 70 that still predict high-risk disease with 97.7% sensitivity[5]. Our data suggest that increasing genetic abnormalities as described by the gene expression data are associated with increased risk for EM relapse
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