Reduced bone marrow stem cell pool and progenitor mobilisation in multiple myeloma after melphalan treatment

The content of stem cells was analysed in bone marrow samples from 75 multiple myeloma patients. In unstimulated bone marrow the percentage of CD34+ cells was significantly reduced in 11 patients previously treated with melphalan-prednisolone (MP)(median= 0.15%) compared to median 0.87% in 31 untreated patients (P=0.0001). The bone marrow cellularity in the two groups did not differ. There was no correlation between the number of courses or total dose of melphalan and content of CD34+ cells in the bone marrow. The clonogenicity as well as the ability to expand the marrow stem cell pool during growth factor treatment were also reduced in MP treated patients compared to untreated patients. Analysis of different subsets of CD34+ cells revealed no influence on the pre B cell compartment in the bone marrow by MP treatment, but the committed stem cells (CD34+CD38+) were reduced more than the uncommitted stem cells (CD34+CD38-) in the MP treated group compared to the untreated patients. Mobilisation to and harvest of total number of CD34+ cells from peripheral blood was also reduced in the MP treated group. There was, however, no difference in the distribution between CD34+CD38+ and CD34+CD38- populations in the leukapheresis products in the untreated and the melphalan-treated group, suggesting selective mobilisation of CD34+CD38+ cells and/or differentiation of CD34+CD38-cells during growth factor stimulation. We conclude that melphalan decreased the number of stem cells in the bone marrow, the ability to expand the stem cell pool and mobilise stem cells to the pheripheral blood.     

Prognostic relevance of CD56 expression in multiple myeloma: a study including 107 cases treated with high-dose melphalan-based chemotherapy and autologous stem cell transplant

CD56 is a neural adhesion molecule and expressed in 70-80% cases of multiple myeloma (MM). Lack of CD56 expression has shown to be a poor prognosis in MM patients treated with conventional chemotherapy, but its prognostic relevance in MM treated with high dose chemotherapy and autologous stem cell transplant (ASCT) is not known. CD56 expression was evaluated by immunohistochemistry on bone marrow paraffin embed specimens from 107 MM cases undergoing Melphalan-based high dose therapy and ASCT. CD56 was expressed by the myeloma cells in 71% of the patients. CD56 negative myeloma was associated with bone lesions ( p = 0.032), but there was no association with any other biological or genetic risk factors including deletions 13q, p53 and IgH translocations, as evaluated by fluorescence in situ hybridization (FISH). There was no significant difference between CD56 positive and CD56 negative myeloma for progression free or overall survival ( p = 0.28 and p = 0.67, respectively). In contrast to reports of CD56 in myeloma treated with conventional chemotherapy, CD56 negativity was not found to confer a poor prognosis in these patients, suggesting Melphalan-based high-dose chemotherapy and ASCT may overcome the adverse influence of CD56 negative myeloma.     

多发性骨髓瘤患者骨髓中Treg细胞与预后相关性研究

目的：检测多发性骨髓瘤（Multiple myeloma,MM）患者及正常人外周血和骨髓Treg细胞水平,评价MM患者骨髓微环境的免疫状态,以及免疫状态与疾病水平的相关性。方法采用流式细胞术检测45例MM患者外周血以及骨髓中Treg细胞水平,15例正常人外周血及骨髓中Treg细胞水平。以CD4^＋CD25high^＋细胞占CD4＋细胞的百分比代表Treg细胞水平。结果 MM患者外周血Treg细胞高于正常人外周血,MM患者骨髓中Treg细胞低于正常人骨髓,MM患者骨髓微环境中Treg细胞降低水平与浆细胞比例无关,而与疾病的预后相关,与β2-MG水平及ISS相关。结论 MM骨髓微环境中肿瘤诱导的免疫系统的改变是MM发病的原因之一,MM患者骨髓中Treg细胞降低比例与预后相关,而与肿瘤负担无关。     

CD117在多发性骨髓瘤细胞中的表达及其意义

背景与目的:细胞表面分化抗原 CD117是酪氨酸激酶选择性抑制剂作用的靶点之一,细胞表面是否表达 CD117及表达的量与酪氨酸激酶选择性抑制剂作用关系密切.本研究探讨 CD117在各种多发性骨髓瘤( multiple myeloma,MM)细胞中的表达,为酪氨酸激酶选择性抑制剂在 MM中的应用提供理论依据,同时评价 CD117在 MM细胞中表达的意义.方法:采用 CD45/SSC双参数散点图设门方法进行三色流式细胞术测定细胞表面分化抗原 CD117、 CD56、 CD54.结果: 48例 MM患者中有 17例( 35.50%)瘤细胞 CD117表达阳性, 39例 (81 20% )CD56表达阳性, 48例 (100 00% )CD54表达阳性, 48例 MM患者瘤细胞 CD117阳性率低于 CD56、 CD54; CD117阳性率与骨髓中瘤细胞比例呈正相关; CD117在 IgG型的 MM中阳性率 (64.00% )高于其它如轻链型、 IgA型 MM; CD117阳性率在不同分期、初治或复发难治的 MM中差异无显著性 (P >0.05, P >0.01); CD117阳性的初治 MM患者对 VAD化疗方案的反应率 (71.43% )与 CD117阴性的反应率 (66.68% )比较无明显差异 (P >0.05).结论: CD117可作为 MM的肿瘤相关抗原, 也可作为靶向信号转导抑制剂酪氨酸激酶选择性抑制剂应用的有价值的标志.     

多发性骨髓瘤患者浆细胞免疫表型特点及其临床意义研究

目的：观察多发性骨髓瘤（MM）患者骨髓中浆细胞免疫表型特点,及其与患者临床预后的相关性。方法：收集35例MM患者资料,骨髓涂片及切片分别经瑞氏-吉姆萨和HE染色后,观察分析骨髓细胞形态及病理学特点。同时,取患者骨髓或外周血分别进行流式细胞术检测及相关实验室检查。结果：MM患者骨髓浆细胞不仅数量明显增多,且形态明显异常,切片中浆细胞分布类型包括塞实型16例（45.71%）,结节型14例（40.00%）和间质型5例（14.29%）。MM患者中出现血清LDH、β2-MG、Cr和BUN等检测指标升高的比例分别占80%、85.71%、62.86%和60%。MM患者浆细胞CD38、CD138均呈阳性表达,CD56、CD200、CD117和CD28阳性患者比例分别为65.71%、94.29%、60%和54.29%,CD20、CD81、CD33、CD27及CD13阳性患者比例分别为37.14%、42.86%、28.57%、57.14%和34.29%,而CD19及CD45阳性患者比例分别为22.86%和31.42%,且Igκ或Igλ链表达缺失呈单克隆增生。其中CD27和CD28的表达情况与MM患者预后密切相关,浆细胞CD27表达缺失及CD28阳性表达的患者5年总生存率较低（P < 0.05）。结论：MM患者骨髓中浆细胞免疫表型明显异常,其中CD27和CD28的表达与患者病情进展和临床预后具有显著相关性,因此免疫表型检测在MM患者临床诊断、治疗监测中具有重要意义。     

多发性骨髓瘤患者浆细胞免疫表型特点及其临床意义研究

目的：观察多发性骨髓瘤（MM）患者骨髓中浆细胞免疫表型特点，及其与患者临床预后的相关性。方法：收集35例MM患者资料，骨髓涂片及切片分别经瑞氏-吉姆萨和HE染色后，观察分析骨髓细胞形态及病理学特点。同时，取患者骨髓或外周血分别进行流式细胞术检测及相关实验室检查。结果：MM患者骨髓浆细胞不仅数量明显增多，且形态明显异常，切片中浆细胞分布类型包括塞实型16例（45.71%），结节型14例（40.00%）和间质型5例（14.29%）。MM患者中出现血清LDH、β2-MG、Cr和BUN等检测指标升高的比例分别占80%、85.71%、62.86%和60%。MM患者浆细胞CD38、CD138均呈阳性表达，CD56、CD200、CD117和CD28阳性患者比例分别为65.71%、94.29%、60%和54.29%，CD20、CD81、CD33、CD27及CD13阳性患者比例分别为37.14%、42.86%、28.57%、57.14%和34.29%，而CD19及CD45阳性患者比例分别为22.86%和31.42%，且Igκ或Igλ链表达缺失呈单克隆增生。其中CD27和CD28的表达情况与MM患者预后密切相关，浆细胞CD27表达缺失及CD28阳性表达的患者5年总生存率较低（P < 0.05）。结论：MM患者骨髓中浆细胞免疫表型明显异常，其中CD27和CD28的表达与患者病情进展和临床预后具有显著相关性，因此免疫表型检测在MM患者临床诊断、治疗监测中具有重要意义。     

骨髓多种检查方法在初诊多发性骨髓瘤中的应用价值

目的:探讨骨髓涂片、骨髓免疫组织化学检查、流式细胞术、荧光原位杂交（FISH）以及细胞遗传学检测在初诊多发性骨髓瘤中的应用价值。方法:收集2018年9月至2019年8月于天津金域医学检验实验室初诊的多发性骨髓瘤患者280例,均按照常规方法进行骨髓穿刺,并进行骨髓涂片、骨髓免疫组织化学检查、流式细胞术免疫分型、FISH、细胞遗传学检测,比较各检测方法的结果。结果:280例患者中,骨髓免疫组织化学检查的中位浆细胞比例高于骨髓涂片（20例,0.675比0.300）及流式细胞术（47例,0.650比0.147）,差异均有统计学意义（ Z=-3.883, P<0.01; Z=-5.947, P<0.01）。流式细胞术检测CD38、CD138、κ、λ、CD56、CD19的阳性率分别为100.0%（280/280）、100.0%（280/280）、57.5%（161/280）、42.5%（119/280）、62.1%（174/280）、19.3%（54/280）;骨髓免疫组织化学检查中CD38、CD138、κ、λ、CD56的阳性率分别为98.9%（277/280）、98.2%（275/280）、57.5%（161/280）、42.5%（119/280）、62.1%（174/280）;两种检测方法对相同检测指标的检测符合率比较,差异均无统计学意义（均 P>0.05）。行FISH检测的患者基因异常检出率为69.9%（93/133）,其中直接荧光原位杂交（D-FISH）异常检出率为42.9%（57/133）,CD138磁珠分选系统（MACS）-FISH异常检出率为82.7%（110/133）。行G显带检测的患者异常染色体核型检出率为38.5%（85/221）。FSIH,尤其是MACS-FISH,细胞遗传学异常检出率高于G显带检测,差异有统计学意义（ χ2=65.697, P<0.05）。 结论:骨髓涂片、骨髓免疫组织化学检查、流式细胞术、FISH（尤其是MACS-FISH）、细胞遗传学等多种检查方法综合应用更有助于多发性骨髓瘤的诊断,并可能对预后判定有一定的意义。     

Dual inhibition of enhancer of zeste homolog 1/2 overactivates WNT signaling to deplete cancer stem cells in multiple myeloma

Multiple myeloma (MM) is an incurable hematological malignancy caused by accumulation of abnormal clonal plasma cells. Despite the recent development of novel therapies, relapse of MM eventually occurs as a result of a remaining population of drug‐resistant myeloma stem cells. Side population (SP) cells show cancer stem cell‐like characteristics in MM; thus, targeting these cells is a promising strategy to completely cure this malignancy. Herein, we showed that SP cells expressed higher levels of enhancer of zeste homolog (EZH) 1 and EZH2, which encode the catalytic subunits of Polycomb repressive complex 2 (PRC2), than non‐SP cells, suggesting that EZH1 as well as EZH2 contributes to the stemness maintenance of the MM cells and that targeting both EZH1/2 is potentially a significant therapeutic approach for eradicating myeloma stem cells. A novel orally bioavailable EZH1/2 dual inhibitor, OR‐S1, effectively eradicated SP cells and had a greater antitumor effect than a selective EZH2 inhibitor in vitro and in vivo, including a unique patient‐derived xenograft model. Moreover, long‐term continuous dosing of OR‐S1 completely cured mice bearing orthotopic xenografts. Additionally, PRC2 directly regulated WNT signaling in MM, and overactivation of this signaling induced by dual inhibition of EZH1/2 eradicated myeloma stem cells and negatively affected tumorigenesis, suggesting that repression of WNT signaling by PRC2 plays an important role in stemness maintenance of MM cells. Our results show the role of EZH1/2 in the maintenance of myeloma stem cells and provide a preclinical rationale for therapeutic application of OR‐S1, leading to significant advances in the treatment of MM.     

MicroRNA‐324‐5p regulates stemness,pathogenesis and sensitivity to bortezomib in multiple myeloma cells by targeting hedgehog signaling

Chromosome 17p deletions are present in 10% of patients with newly diagnosed multiple myeloma (MM), and are associated with inferior prognosis. miR‐324‐5p is located on chromosome 17p, and shows diverse functions in different types of cancers. However, its role in MM is largely unknown. Here we found the expression of miR‐324‐5p was decreased in MM, especially in del(17p) MM. In contrast, the expression of hedgehog (Hh) signaling components was elevated, indicating a correlation between miR‐324‐5p and Hh signaling in MM. Hh signaling is important for the pathogenesis of MM and maintenance of MM stem cell compartment. Indeed, overexpression of miR‐324‐5p significantly decreased Hh signaling components Smo and Gli1, and functionally reduced cell growth, survival as well as stem cell compartment in MM. Moreover, miR‐324‐5p potentiated the anti‐MM efficacy of bortezomib through regulating the activities of multidrug‐resistance proteins and the expression of Bcl‐2 family genes. Consistent results were obtained in vivo. Finally, miR‐324‐5p overcame the protective effect of bone marrow stromal cells on MM cells. Taken together, our data demonstrate that miR‐324‐5p is essential for MM pathogenesis and downregulation of miR‐324‐5p is a novel mechanism of Hh signaling activation in MM. Therefore, targeting miR‐324‐5p provides a potential therapeutic strategy for MM.     

多发性骨髓瘤患者OPN、CD44v6的表达与病情进展的关系

背景与目的:骨桥蛋白(osteopontin,OPN)与其受体--CD44受体和整合素受体结合后,参与骨重建、骨质重吸收、血管重塑、癌细胞浸润和转移等过程.为此本研究检测了多发性骨髓瘤(multiple myeloma,MM)患者的OPN和变异的CD44受体(CD44v6)水平,以探讨其与MM病情进展的关系.方法:32例MM患者,分为A组(包括初发和复发病例)和B组(化疗后病情稳定)2组,同时收集外伤骨折或非肿瘤良性贫血患者15例作为对照.采用酶链免疫吸附试验(ELISA)分别检测了患者和对照组的单个核细胞及骨髓基质细胞(bone marrow mononuclear eells,BMSCs)培养上清液的0PN、CD44v6水平并进行相关分析.结果:A组(19例)患者的0PN表达水平显著高于B组(13例)和对照组患者(P<0.05).对A组中的14例患者和B组中的10例患者进行了CD44v6水平检测,其结果A组的CD44v6表达水平显著高于B组和对照组患者(P<0.05),B组的CD44v6水平显著高于对照组(P<0.05);0PN水平与CD44v6(r=0.52,P=0.000)、恶性浆细胞数(r=0.74,P=0.000)、M蛋白水平(r=0.53,P=0.014)、血β2-MG水平(r=0.62,P=0.002)均呈正相关.结论:0PN和CD44v6水平升高与删的发生和病情进展有关;可能与MM的肿瘤负荷、疾病阶段和肿瘤浸润有关.     

Bone marrow derived dendritic cells from patients with multiple myeloma cultured with three distinct protocols do not bear Kaposi's sarcoma associated herpesvirus DNA

Background: An association between Kaposi's sarcoma associated herpesvirus (KSHV) and the pathogenesis of multiple myeloma (MM) was postulated recently. The dendritic cells of patients with MM were proposed to be infected with the virus.Patients and methods: Bone marrow mononuclear cells (MNC) of 23 patients, 22 with MM and one with MGUS, were cultured according to three distinct protocols for the generation of dendritic cells. One was essentially the stromal cell culture protocol described by Rettig et al. (Science 1997; 276: 1851–4), while the two other protocols comprised growth factors. Cultured cells were characterised by FACS analysis and assessed for the presence of KSHV DNA with a highly sensitive and specific nested PCR assay detecting the KS 330233 sequence of the virus genome followed by hybridisation with a KSHV specific oligonucleotide.Results: FACS analysis of the cells with the specific markers CD1a, CD86 and HLA-DR, characteristic for dendritic cells, revealed differences in the expression pattern depending on the protocol used. The proportion of CD1a+ cells was very low in the stromal cell cultures (median 0.4%), while a higher percentage of CD14+ cells could be observed (median 37.8%). Growth factor containing cultures revealed a distinctly higher median percentage of CD1a+ cells of 32.5%. The proportion of CD86+ cells varied between 10.4% and 78.5% and HLA-DR+ cells between 26% and 94.4%. Examination of those cells with PCR did not reveal positivity for KSHV in any of the 34 samples assessed. Amplification of seven samples revealed PCR products of approximately the size of the KS 330233, which, however, could not be confirmed as KSHV specific after hybridisation.Conclusion: We have no evidence that bone marrow derived dendritic cells from patients with MM are infected with KSHV.     

多发性骨髓瘤患者骨髓间充质干细胞体外生长特性和转化生长因子-β1基因的表达及其意义

  目的　探讨多发性骨髓瘤（ MM）患者骨髓间充质干细胞（BMMSC）体外生长特性和转化生长因子-β1（TGF-β1）基因表达变化及意义。方法　以7例MM患者为试验组（MM组）,10例单纯缺铁性贫血患者为对照组,取骨髓单个核细胞进行BMMSC 体外培养,观察BMMSC 体外生长形态并计数,绘制生长曲线。取BMMSC 提取总RNA,反转录-聚合酶链反应（RT-PCR）法测定两组BMMSC 中TGF-β1 mRNA表达水平。结果　MM患者BMMSC 生长活性与对照组无明显差别;MM组BMMSC中TGF-β1 mRNA表达水平（0.01241±0.00419）较对照组（0.00122±0.00030）升高,差异有统计学意义（t＝3.218,P＜0.05）。结论　MM患者BMMSC中TGF-β1高表达可能与MM发病有关。     

Argonaute 2与多发性骨髓瘤血管生成临床关系研究

目的 了解Argonaute 2(Ago2)在多发性骨髓瘤(MM)骨髓组织中的表达水平,探讨其与骨髓内血管生成的关系.方法 应用改良的甲基丙烯酸甲酯(MMA)单体塑料包埋法对59例MM患者及16例正常对照进行骨髓活组织检查的组织制片,采用EnVision免疫组织化学二步法检测MM患者及正常对照骨髓组织中Ago2蛋白表达水平及微血管密度(MVD),并用Western blot方法检测8例MM患者和3例正常对照Ago2蛋白表达水平.结果 Western blot检测显示,Ago2蛋白在MM患者骨髓组织中表达高于正常对照(1.35±0.19比0.15±0.03,t=-19.883,P＜0.001).免疫组织化学结果表明,59例MM患者骨髓组织中Ago2蛋白阴性和阳性分别为9例和50例,对照组16例均为阴性,两组差异有统计学意义(x2=42.586,P＜ 0.001).MM患者中,Ago2阳性组β2-微球蛋白高于阴性组,差异有统计学意义(Z=-2.014,P=0.042).MM患者骨髓组织中MVD为7.89±4.88,正常对照组为2.16±1.32,两组之间差异有统计学意义(t=4.63,P＜0.001).MM患者骨髓组织中Ago2蛋白表达水平与MVD具有相关性(r=0.461,P=0.023).Ago2蛋白阳性组MVD较阴性组增高,差异有统计学意义(t=2.71,P=0.009).结论 Ago2在MM患者骨髓组织中表达水平明显升高,可能参与了MM患者的病理发生,并对骨髓内异常新生血管生成起一定的调节作用.     

多发性骨髓瘤患者基质细胞衍生因子-1α、CD44v6表达的研究

 目的　探讨基质细胞衍生因子-1α（SDF-1α）、CD44v6（一种变异的CD44受体）在多发性骨髓瘤（MM）中的表达水平及其与病情进展的关系。方法　用酶联免疫吸附试验（ELISA）检测24例MM患者[14例初发和复发MM患者（初发和复发MM组）,10例病情稳定MM患者（病情稳定MM组）]和15位健康骨髓移植供者或非肿瘤良性贫血患者（对照组）的骨髓单个核细胞（MNC）和骨髓基质细胞（BMSC）培养上清的SDF-1α、CD44v6水平。结果　初发和复发MM组MNC培养上清的SDF-1α、CD44v6表达水平[（7232.41±2644.97）pg／ml和（34.34±13.20）ng／ml]显著高于病情稳定MM组[（2315.49±748.29）pg／ml和（15.69±5.28）ng／ml]（t＝6.25、t＝7.82;均P＜0.05）和对照组[（1149.52±636.06）pg／ml和（4.85±3.62）ng／ml]（t＝4.60、t＝7.61;均P＜0.05）。病情稳定MM组SDF-1α、CD44v6水平显著高于对照组（t＝2.99、t＝4.87;均P＜0.05）。9例初发和复发MM组的BMSC与人类骨髓瘤细胞系细胞U266加入rhIL-6进行混合培养后,SDF-1α水平[（6180.25±5925.38）pg／ml]显著高于5例对照组BMSC[（1021.13±358.65）pg／ml]和9例初发和复发MM组[（1004.07±727.36）pg／ml]（t＝2.66、t＝2.42;均P＜0.05）。而其他BMSC各组间的SDF-1α水平差异无统计学意义（P＞0.05）。SDF-1α与CD44v6两者表达水平呈正相关（r＝0.51,P＝0.03）。结论　SDF-1α、CD44v6水平升高与MM的病情进展或发病有关,也可能与MM的肿瘤浸润过程有关;而这些体内过程可能需骨髓瘤细胞和BMSC与IL-6、SDF-1α和CD44v6等因素协同完成。     

多发性骨髓瘤伴髓外病变研究进展

多发性骨髓瘤（MM）是一种以分泌单克隆免疫球蛋白或其片段（M蛋白）为特征的恶性浆细胞疾病。一般情况下,骨髓瘤细胞局限于髓内,但在初诊或疾病进展过程中均可出现髓外病变（EM）,伴EM的MM患者预后较差。根据EM的发生方式可将其分为单纯骨相关髓外病变（EM-b）和软组织相关髓外病变（EM—s）。EM—b为骨髓瘤细胞突破骨皮质累及周围连续性软组织的病变;EM-s为通过血源播散到髓外的软组织或其他器官的病变。研究发现不论是初诊MM还是疾病进展过程中发生的EM-s,其预后都比EM-b差。因此,文章主要综述EM-b和EM-S的区别,包括两者的发病率、生物学特征、临床表现、治疗及预后。     

Tumour Kinetics in Multiple Myeloma Before, During, and After Treatment

Tumour progression was monitored in seven multiple myeloma (MM) patients undergoing a novel oral chemotherapy regimen (cyclophosphamide, idarubicin and dexamethasone; CID) followed by early autologous stem cell transplantation (ASCT). Allele-specific oligonucleotide PCR (ASO-PCR) was used to semi-quantitate the number of tumour cells within the peripheral blood (PB) and PB progenitor cell (PBPC) harvests and compared with paraprotein levels and morphological bone marrow (BM) assessments. Tumour cells were detected in the PB of all patients at diagnosis, but decreased in response to CID therapy. All but two of the 22 PBPC collections contained MM cells, the levels of which were statistically correlated with overall clinical response to therapy, but not with individual BM or PB tumour loads prior to mobilisation. We also found no correlation between the day of leucapheresis collection and the number of contaminating MM cells, CD34⁺ cells or MM cells per CD34⁺ cell. Regardless of tumour contamination levels in the PBPC collections, the majority of patients demonstrated post-ASCT clearing of circulating MM cells. This study suggests that levels of circulating MM cells may be the best indication of patient response to treatment and argues against the theory of differential mobilisation of tumour cells and CD34⁺cells in response to cytokine treatment.     

组织因子在多发性骨髓瘤中的表达及其与血管新生的关系

 目的　研究多发性骨髓瘤（MM）患者骨髓组织中组织因子（TF）的表达及其与血管内皮生长因子（VEGF）和骨髓血管新生程度的关系。方法　采用免疫组织化学法对试验组32例初治／复发的MM患者、对照组32例缺铁性贫血患者和健康者骨髓组织的TF、VEGF表达水平和微血管密度（MVD）进行测定。结果　试验组与对照组的TF、VEGF阳性率分别为88 %、78 %;60 %、10 %。试验组与对照组TF、VEGF中位表达水平分别为（++） 、（++）;（-）、（-）;试验组与对照组中位MVD分别为4、0。试验组TF表达水平与血管新生程度等级相关性分析结果显示TF表达水平与血管新生程度呈等级正相关（rs＝0.568,P＜0.001）。结论　MM患者骨髓组织中的TF表达水平与VEGF表达水平高于对照组,与血管新生程度呈等级正相关。     

CXCR4 is a good survival prognostic indicator in multiple myeloma patients

SDF-1α and its receptor CXCR4 are involved in multiple myeloma (MM) by attracting and activating plasma cells in the bone marrow. CXCR4 expression in MM cells is inversely correlated with disease activity. The aim of this study was to evaluate CXCR4 as a prognostic tool in MM, as well as other markers of disease, such as chromosomal aberrancies. Purpose was to investigate the expression levels of SDF-1α before and after bortezomib and thalidomide treatment. From February 2006 to April 2012, CXCR4 expression was prospectively assessed in bone marrow samples from a large population of patients (n = 227) using flow cytometry. Clinical characteristics were collected and chromosomal aberrancies were assessed in 144 patients. SDF-1α levels were determined using ELISA in peripheral blood samples from 40 patients before and after chemotherapy. Our results show that CXCR4 was present in 43.2% (98/227) of newly diagnosed MM patients and that CXCR4 expression was significantly correlated with CD117 (P < 0.05). CXCR4-positive MM patients had a significantly longer estimated survival time than CXCR4-negative patients (median of 48 vs. 42 months, P < 0.05). Multivariate survival analyses identified that the +1q21/CXCR4− phenotype is an independent survival predictor, along with the International Staging System (ISS) stage. No significant difference was observed in expression levels of SDF-1α before and after bortezomib/thalidomide treatment. In conclusion, +1q21/CXCR4− could be an independent survival prognosis predictor in MM patients. Expression levels of SDF-1α before and after bortezomib/thalidomide treatment are not different, although they are higher than in controls.