An MDS-derived cell line and a series of its sublines serve as an in vitro model for the leukemic evolution of MDS
An MDS-derived cell line and a series of its sublines serve as an in vitro model for the leukemic evolution of MDS
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DOI：
10.1038/s41375-018-0189-7
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发表时间：
2018-08-01
期刊：
影响因子：
11.4
通讯作者：
Tohyama, Kaoru
中科院分区：
文献类型：
--
作者：
Kida, Jun-ichiro;Tsujioka, Takayuki;Tohyama, Kaoru
骨髓增生异常综合征（MDS）是一种克隆性造血干细胞疾病，其特征是造血功能低下和进展为急性髓性白血病（AML）的风险增加。体细胞突变的发生导致分化受损的异常克隆的形成，额外的驱动突变最终导致AML[1]。我们之前从5q染色体缺失的MDS患者的骨髓中建立了骨髓增生异常细胞系MDS92 [del (5q)][2,3]。MDS92细胞在白细胞介素(IL)-3存在下增殖，具有逐渐成熟的趋势，并表现出核型异常，包括del (5q)(实际上是der（5)(5; 19)）、单体7和NRAS基因[2]密码子12点突变。这些特性与MDS的特性完全兼容。后来，在mds92[4]的基础上，又建立了塑性子线MDS-L。MDS- l细胞系为MDS的del (5q)[5,6]和来那度胺治疗机制的研究做出了贡献[4,7]。MDS- l也被用作免疫缺陷小鼠[8]的体内模型，并被用于研究各种有望治疗MDS的药物[9,10]。除了MDS-L外，我们还从亲本MDS92中分离出了几个相互独立的母细胞亚系，并进一步从MDS-L中分别获得了IL-3存在和不存在的MDS-L-2007和MDS-LGF（图1a）。细胞系的形态和表面标记见附录
Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and increased risk of progression to acute myeloid leukemia (AML). Occurrence of somatic mutations leads to formation of an abnormal clone with impaired differentiation, and additional driver mutations lead finally to AML [1]. We previously established a myelodysplastic cell line MDS92 from the bone marrow of an MDS patient with deletion of 5q chromosome [del (5q)][2, 3]. MDS92 cells proliferated in the presence of interleukin (IL)-3 with a tendency for gradual maturation and represented karyotypic abnormalities including del (5q)(actually der (5)(5; 19)), monosomy7, and a point mutation at codon12 of NRAS gene [2]. These characteristics are exclusively compatible with the property of MDS. Later, a blastic subline MDS-L was established from MDS92 [4]. MDS-L cell line has contributed to the molecular study of MDS with del (5q)[5, 6] and therapeutic mechanisms of lenalidomide [4, 7]. MDS-L has also been utilized as an in vivo model by transplanting experiments into immunodeficient mice [8] and for investigation of various drugs expected for treatment of MDS [9, 10]. In addition to MDS-L, we isolated several blastic sublines independently of one another from the parental MDS92, and further obtained MDS-L-2007 and MDS-LGF from MDS-L in the presence and absence of IL-3, respectively (Fig. 1a). The morphology and surface markers of the cell lines are shown in Supplementary