Bone marrow stromal mesenchymal cells induce down regulation of CD20 expression on B-CLL: implications for rituximab resistance in CLL
Bone marrow stromal mesenchymal cells induce down regulation of CD20 expression on B-CLL: implications for rituximab resistance in CLL
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DOI：
10.1111/bjh.13286
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发表时间：
2015-04-01
影响因子：
6.5
通讯作者：
Da Costa, Osiris
中科院分区：
文献类型：
--
作者：
Marquez, Maria-Elena;Hernandez-Uzcategui, Octavio;Da Costa, Osiris
虽然大多数B细胞在慢性淋巴细胞白血病（B- cll）中表达表面CD20，但只有约50%的患者对美罗华治疗有反应。在一些接受利妥昔单抗治疗的患者中，这些肿瘤B细胞上CD20表达的降低可能是缺乏反应的原因。尽管CD20在B细胞恶性肿瘤的生物学中具有潜在的关键作用，但控制其表达的机制尚不清楚。在骨髓水平，间充质基质细胞（MSC）可能调节和支持恶性细胞的存活，如B-CLL细胞。在这项研究中，我们研究了MSC是否可以调节CD20在B-CLL中的表达。为此，分离CLL患者的B细胞并在MSC上共培养。从B-CLL/MSC共培养中收集B-CLL细胞，检测其CD20的表达。我们发现，在与MSC共培养2周后，在接触和非接触条件下，B-CLL细胞中CD20表达降低，这与对利妥昔单抗的敏感性降低有关。此外，与MSCs共培养的B细胞显示CD59表达增加。我们的研究结果强烈提示，B-CLL细胞和MSC之间的相互作用可能在利妥昔单抗诱导的B-CLL细胞凋亡的抗性中起主要作用。
Although the majority of B cells express surface CD20 in chronic lymphocytic leukaemia (B-CLL), only approximate to 50% of patients respond to treatment with rituximab. Decreased CD20 expression on these tumour B cells could be responsible for the lack of response observed in some patients treated with rituximab. Despite the potential critical role of CD20 in the biology of B cell malignancies, the mechanisms controlling its expression are poorly understood. At the bone marrow level, mesenchymal stromal cells (MSC) may regulate and support the survival of malignant cells, such as B-CLL cells. In this study, we investigated whether MSC may regulate the CD20 expression on B-CLL. For this purpose, B cells from CLL patients were isolated and co-cultured on MSC. B-CLL cells were collected from B-CLL/MSC co-cultures and examined for their expression of CD20. We demonstrate decreased CD20 expression in B-CLL cells after 2weeks of co-culture with MSC, under contact and non-contact conditions, which was associated with a decreased susceptibility to rituximab. Additionally, B cells co-cultured with MSCs show an increase in CD59 expression. Our findings strongly suggest that the interaction between B-CLL cells and MSC may play a major role in the resistance to rituximab-induced apoptosis of B-CLL cells.