Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015, 159(2):288-293 | DOI: 10.5507/bp.2015.014

Extramedullary relapse of multiple myeloma defined as the highest risk group based on deregulated gene expression data

Sabina Sevcikova^a,b, Helena Paszekova^c, Lenka Besse^a,b, Lenka Sedlarikova^a,b, Veronika Kubaczkova^a, Martina Almasi^a,b, Ludek Pour^d, Roman Hajek^a,b,e

^a Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic

^b Department of Clinical Hematology, University Hospital Brno

^c Institute of Pathological Physiology, 1^st Faculty of Medicine, Charles University in Prague

^d Department of Internal Medicine - Hematooncology, University Hospital Brno

^e Department of Clinical Studies, Faculty of Medicine, University of Ostrava

Background: 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.

Aims: 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.

Methods: 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.

Results: 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).

Conclusions: Our data suggest that increasing genetic abnormalities as described by the gene expression data are associated with increased risk for EM relapse.

Keywords: multiple myeloma, gene expression, high-risk disease, extramedullary relapse, qPCR

Received: November 7, 2014; Accepted: March 31, 2015; Prepublished online: April 16, 2015; Published: June 28, 2015  Show citation