儿童急性淋巴细胞白血病中骨髓间充质基质细胞的生物学特性
Biological Features of Bone Marrow Mesenchymal Stromal Cells in Childhood Acute Lymphoblastic Leukemia.
作者信息
Genitsari Stella, Stiakaki Eftichia, Perdikogianni Chryssoula, Martimianaki Georgia, Pelagiadis Iordanis, Pesmatzoglou Margarita, Kalmanti Maria, Dimitriou Helen
机构信息
Crete University Faculty of Medicine, University Hospital of Heraklion, Department of Pediatric Hematology and Oncology, Crete, Greece.
Crete University Faculty of Medicine, Department of Pediatrics, Crete, Greece.
出版信息
Turk J Haematol. 2018 Mar 1;35(1):19-26. doi: 10.4274/tjh.2017.0209. Epub 2017 Sep 8.
OBJECTIVE
Mesenchymal stromal cells (MSCs) have a supportive role in hematopoiesis and as components of the bone marrow (BM) microenvironment may present alterations during acute lymphoblastic leukemia (ALL) and be affected by chemotherapeutic agents. We examined the biological and functional characteristics of MSCs in ALL diagnosis and treatment and their effect on MSC qualitative properties.
MATERIALS AND METHODS
Immunophenotypic characterization, evaluation of clonogenicity, and proliferative capacity were measured. Apoptotic features, cell-cycle analysis, and stromal cell-derived factor 1α and angiopoietin-1 levels in MSC supernatant at diagnosis and in different phases of treatment were assessed. Chemotherapy was administered according to the Berlin-Frankfurt-Munster-2000 protocol. BM samples from children with solid tumors without BM involvement were used as the control group.
RESULTS
The morphology, the immunophenotypic profile, and the apoptotic characteristics of the MSCs were not affected by leukemia. The secretion of factors involved in the trafficking of hematopoietic cells in the BM seems to be upregulated at diagnosis in comparison to the treatment phases. MSCs are influenced by the disease in terms of their functional characteristics such as clonogenicity and proliferation rate. These effects cease as soon as treatment is initiated. Chemotherapy does not seem to exert any effect on any of the MSC features examined.
CONCLUSION
MSCs from children with ALL are affected by their interaction with the leukemic environment, but this phenomenon ceases upon treatment initiation, while no effect is observed by chemotherapy itself.
目的
间充质基质细胞(MSCs)在造血过程中起支持作用,作为骨髓(BM)微环境的组成部分,在急性淋巴细胞白血病(ALL)期间可能会出现改变,并受到化疗药物的影响。我们研究了MSCs在ALL诊断和治疗中的生物学和功能特性及其对MSC定性特性的影响。
材料和方法
测定免疫表型特征、克隆形成能力评估和增殖能力。评估诊断时和治疗不同阶段MSC上清液中的凋亡特征、细胞周期分析以及基质细胞衍生因子1α和血管生成素-1水平。根据柏林-法兰克福-明斯特-2000方案进行化疗。将无BM受累的实体瘤患儿的BM样本用作对照组。
结果
白血病未影响MSCs的形态、免疫表型特征和凋亡特征。与治疗阶段相比,BM中参与造血细胞运输的因子分泌在诊断时似乎上调。MSCs的功能特性如克隆形成能力和增殖率受到疾病的影响。一旦开始治疗,这些影响就会停止。化疗似乎对所检测的任何MSC特征均无影响。
结论
ALL患儿的MSCs受到其与白血病环境相互作用的影响,但这种现象在开始治疗后停止,而化疗本身未观察到任何影响。
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