Hu Wen-Tan, Liu Jun-Wen, Liu Hong-Chun, Wang Ting-Ting
Department of Clinical Laboratorial Examination,The First Affiliated Hospital of Zhengzhou University; Key Laboratory of Henan Provicial Clinical Laboratorial Medicine; Department of Clinical Laboratorial Medicine of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
Department of Clinical Laboratorial Examination,The First Affiliated Hospital of Zhengzhou University; Key Laboratory of Henan Provicial Clinical Laboratorial Medicine; Department of Clinical Laboratorial Medicine of Zhengzhou University, Zhengzhou 450052, Henan Province, China. E-mail:xingyunerliu@163.com.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Oct;24(5):1443-1448. doi: 10.7534/j.issn.1009-2137.2016.05.029.
To investigate the expression level of B lymphocyte-induced maturation protein-1(Blimp-1) mRNA in bone marrow mononuclear cells(BMMNC) of multiple myeloma(MM) patients and its clinical significance.
Fluorescent quantitative real-time PCR(qRT-PCR) was used to measure Blimp-1 mRNA expression in BMMNC and flow cytometry(FCM) was performed to detect the number of malignant plasma cells in bone marrow of MM group (39 newly-diagnosed and untreated patients) and IDA group (5 IDA patients). The clinical data of all the patients' were collected, and the 39 patients in MM group were divided into 2 subgroups: in BD group 20 cases were treated with bortezomib-based regimen and in VOD group 19 patients were treated with VAD regimen. The age, sex, clinseal stage and type between the 2 subgroups were not statistically different. Blimp-1 mRNA expression level in BMMNC of MM patients was detected by qRT-PCR after 3 treatment cycles.
The expression levels of Blimp-1 mRNA in BMMNC of IDA patients and MM patients divided into 3 groups according to ISS were (0.00047±0.00027), ISS I(0.09543±0.02800), Ⅱ(0.13606±0.04162),Ⅲ (0.21202±0.03940), separately. There was statistical difference among the 4 groups(F=56.929,P<0.05) and there was significant difference between any 2 groups of these 4 groups(P<0.05). Significant positive correlation was found between Blimp-1 mRNA expression level and the number of malignant plasma cells, serum monoclonal proteins (M protein), β2-microglobulin(β2-MG), lactic dehydrogenase(LDH), C-reactive protein(CRP)(P<0.05). There was significant negative correlation between Blimp-1 mRNA and hemoglobin (Hb) level (P<0.05). After 3 cycles of chemotherapy, Blimp-1 mRNA level of patients with a >50% reduction of M protein was significantly lower than that of patients whose M protein did not decrease significantly(P<0.05). After 3 treatment cycles, Blimp-1 mRNA expression in BMMNC in BD group was significantly lower than that in VAD group [(0.02388±0.00871) vs (0.04823±0.00219), P<0.05].
The Blimp-1 mRNA expression level in BMMNC may reflect the tumor burden in MM patients, which related with ISS, and positively correlated with the malignant plasma cell number, M protein, β2-MG, LDH, CRP level, and negatively correlated with Hb. The change of Blimp-1 mRNA expression level in BMMNC relates with the extent of M protein reduction, suggesting it may be used as a marker for response to therapy. Bortezomib may have effect on malignant plasma cells by suppressing Blimp-1 mRNA expression.
探讨多发性骨髓瘤(MM)患者骨髓单个核细胞(BMMNC)中B淋巴细胞诱导成熟蛋白-1(Blimp-1)mRNA的表达水平及其临床意义。
采用荧光定量实时PCR(qRT-PCR)检测BMMNC中Blimp-1 mRNA的表达,应用流式细胞术(FCM)检测MM组(39例初诊未治疗患者)及缺铁性贫血(IDA)组(5例IDA患者)骨髓中恶性浆细胞数量。收集所有患者的临床资料,MM组39例患者分为2个亚组:硼替佐米方案组(BD组)20例,采用以硼替佐米为基础的方案治疗;VAD方案组(VOD组)19例,采用VAD方案治疗。2个亚组患者的年龄、性别、临床分期及类型差异无统计学意义。3个治疗周期后,采用qRT-PCR检测MM患者BMMNC中Blimp-1 mRNA表达水平。
IDA患者及按国际分期系统(ISS)分为3组的MM患者BMMNC中Blimp-1 mRNA表达水平分别为(0.00047±0.00027)、ISS I期(0.09543±0.02800)、Ⅱ期(0.13606±0.04162)、Ⅲ期(0.21202±0.03940)。4组间差异有统计学意义(F=56.929,P<0.05),4组中任意2组间差异均有统计学意义(P<0.05)。Blimp-1 mRNA表达水平与恶性浆细胞数量、血清单克隆蛋白(M蛋白)、β2微球蛋白(β2-MG)、乳酸脱氢酶(LDH)、C反应蛋白(CRP)呈显著正相关(P<0.05),与血红蛋白(Hb)水平呈显著负相关(P<0.05)。化疗3个周期后,M蛋白降低>50%患者的Blimp-1 mRNA水平显著低于M蛋白降低不明显患者(P<0.05)。3个治疗周期后,BD组BMMNC中Blimp-1 mRNA表达显著低于VAD组[(0.02388±0.00871)比(0.04823±0.00219),P<0.05]。
BMMNC中Blimp-1 mRNA表达水平可反映MM患者的肿瘤负荷,与ISS相关,与恶性浆细胞数量、M蛋白、β2-MG、LDH、CRP水平呈正相关,与Hb呈负相关。BMMNC中Blimp-1 mRNA表达水平的变化与M蛋白降低程度有关,提示其可能作为疗效反应的标志物。硼替佐米可能通过抑制Blimp-1 mRNA表达对恶性浆细胞产生作用。