Durie B G M, Van Ness B, Ramos C, Stephens O, Haznadar M, Hoering A, Haessler J, Katz M S, Mundy G R, Kyle R A, Morgan G J, Crowley J, Barlogie B, Shaughnessy J
Hematology/Oncology, Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute & Aptium Oncology, Los Angeles, CA 90048, USA.
Leukemia. 2009 Oct;23(10):1913-9. doi: 10.1038/leu.2009.129. Epub 2009 Aug 6.
Bone disease in myeloma occurs as a result of complex interactions between myeloma cells and the bone marrow microenvironment. A custom-built DNA single nucleotide polymorphism (SNP) chip containing 3404 SNPs was used to test genomic DNA from myeloma patients classified by the extent of bone disease. Correlations identified with a Total Therapy 2 (TT2) (Arkansas) data set were validated with Eastern Cooperative Oncology Group (ECOG) and Southwest Oncology Group (SWOG) data sets. Univariate correlates with bone disease included: EPHX1, IGF1R, IL-4 and Gsk3beta. SNP signatures were linked to the number of bone lesions, log(2) DKK-1 myeloma cell expression levels and patient survival. Using stepwise multivariate regression analysis, the following SNPs: EPHX1 (P=0.0026); log(2) DKK-1 expression (P=0.0046); serum lactic dehydrogenase (LDH) (P=0.0074); Gsk3beta (P=0.02) and TNFSF8 (P=0.04) were linked to bone disease. This assessment of genetic polymorphisms identifies SNPs with both potential biological relevance and utility in prognostic models of myeloma bone disease.
骨髓瘤中的骨病是骨髓瘤细胞与骨髓微环境之间复杂相互作用的结果。使用包含3404个单核苷酸多态性（SNP）的定制DNA芯片来检测根据骨病程度分类的骨髓瘤患者的基因组DNA。与总疗法2（TT2）（阿肯色州）数据集确定的相关性在东部肿瘤协作组（ECOG）和西南肿瘤协作组（SWOG）数据集上得到验证。与骨病的单变量相关性包括：EPHX1、IGF1R、IL-4和Gsk3β。SNP特征与骨病变数量、log(2) DKK-1骨髓瘤细胞表达水平和患者生存率相关。使用逐步多元回归分析，以下SNP：EPHX1（P=0.0026）；log(2) DKK-1表达（P=0.0046）；血清乳酸脱氢酶（LDH）（P=0.0074）；Gsk3β（P=0.02）和TNFSF8（P=0.04）与骨病相关。这种基因多态性评估确定了在骨髓瘤骨病预后模型中具有潜在生物学相关性和实用性的SNP。
