Sevcikova Sabina, Paszekova Helena, Besse Lenka, Sedlarikova Lenka, Kubaczkova Veronika, Almasi Martina, Pour Ludek, Hajek Roman
Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Department of Clinical Hematology, University Hospital Brno.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015 Jun;159(2):288-93. doi: 10.5507/bp.2015.014. Epub 2015 Apr 16.
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.
多发性骨髓瘤（MM）的特征是浆细胞（PC）恶性增殖并积聚于骨髓（BM）中。新药的出现已将该疾病的病程从无法治愈转变为可治疗，但大多数患者最终仍会复发。一组MM患者（10 - 15%）被认为是高危患者，因为他们在24个月内复发。最近，MM的髓外复发（EM）观察得更为频繁。由于其侵袭性和较短的生存期，EM也被视为高危情况。
本研究的目的是确定阿肯色大学研究团队（UAMS）公布的所谓高危基因在EM患者中是否比高危MM患者中更失调，以及这些患者是否可被视为高危患者。
使用了9例MM患者的骨髓浆细胞样本以及9例EM患者的肿瘤和9例骨髓浆细胞样本。采用定量实时PCR评估与MM患者高危特征相关的15个基因的表达。
高危浆细胞与髓外浆细胞的比较显示有4个基因显著失调（CKS1B、CTBS、NADK、YWHAZ）；此外，髓外浆细胞与髓外肿瘤的比较显示15个基因中有9个存在显著差异。其中，6个基因显示出与UAMS研究团队所描述的显著变化一致（ASPM、SLC19A1、NADK、TBRG4、TMPO和LARS2）。
我们的数据表明，基因表达数据所描述的遗传异常增加与EM复发风险增加相关。
