文章：

源自急性髓系白血病骨髓的间充质基质细胞表现出异常细胞遗传学和细胞因子分泌

Mesenchymal stromal cells derived from acute myeloid leukemia bone marrow exhibit aberrant cytogenetics and cytokine elaboration

原文发布日期：2015-04-10

DOI: 10.1038/bcj.2015.17

类型: Original Article

开放获取: 是

英文摘要：

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) play a fundamental role in the BM microenvironment (BME) and abnormalities of these cells may contribute to acute myeloid leukemia (AML) pathogenesis. The aim of the study was to characterize the cytokine and gene expression profile, immunophenotype and cytogenetics of BM-MSCs from AML patients compared to normal BM-MSCs from healthy donors. AML BM-MSCs showed decreased monocyte chemoattractant protein-1 levels compared to normal BM-MSCs. AML BM-MSCs expressed similar β1 integrin, CD44, CD73, CD90 and E-cadherin compared to normal BM-MSCs. Cytogenetic analysis revealed chromosomal aberrations in AML BM-MSCs, some overlapping with and others distinct from their corresponding AML blasts. No significant difference in gene expression was detected between AML BM-MSCs compared to normal BM-MSCs; however, comparing the differences between AML and MSCs from AML patients with the differences between normal hematopoietic cells and normal MSCs by Ingenuity pathway analysis showed key distinctions of the AML setting: (1) upstream gene regulation by transforming growth factor beta 1, tumor necrosis factor, tissue transglutaminase 2, CCAAT/enhancer binding protein alpha and SWItch/Sucrose NonFermentable related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; (2) integrin and interleukin 8 signaling as overrepresented canonical pathways; and (3) upregulation of transcription factors FBJ murine osteosarcoma viral oncogene homolog and v-myb avian myeloblastosis viral oncogene homolog. Thus, phenotypic abnormalities of AML BM-MSCs highlight a dysfunctional BME that may impact AML survival and proliferation.

摘要翻译： 

骨髓来源的间充质基质细胞（BM-MSCs）在骨髓微环境（BME）中发挥重要作用，这些细胞的异常可能促进急性髓系白血病（AML）的发病机制。本研究旨在比较AML患者与健康供者正常BM-MSCs的细胞因子和基因表达谱、免疫表型及细胞遗传学特征。与正常BM-MSCs相比，AML BM-MSCs表现出单核细胞趋化蛋白-1水平降低。AML BM-MSCs在β1整合素、CD44、CD73、CD90和E-钙黏蛋白表达方面与正常BM-MSCs相似。细胞遗传学分析显示AML BM-MSCs存在染色体畸变，部分与其对应的AML原始细胞重叠，部分则具有独特性。AML BM-MSCs与正常BM-MSCs之间的基因表达未见显著差异；但通过Ingenuity通路分析比较AML患者AML细胞与MSCs的差异，以及正常造血细胞与正常MSCs的差异，揭示了AML环境的关键特征：（1）转化生长因子β1、肿瘤坏死因子、组织转谷氨酰胺酶2、CCAAT/增强子结合蛋白α及SWItch/蔗糖非发酵相关染色质调控因子a亚族成员4的上游基因调控；（2）整合素和白介素8信号通路作为过度代表的经典通路；（3）转录因子FBJ鼠骨肉瘤病毒癌基因同源物和v-myb禽髓母细胞瘤病毒癌基因同源物的上调。因此，AML BM-MSCs的表型异常揭示了功能失调的BME，这可能影响AML的存活与增殖。

原文链接：

Mesenchymal stromal cells derived from acute myeloid leukemia bone marrow exhibit aberrant cytogenetics and cytokine elaboration