Development of a model for evaluating the interaction between human pre-B acute lymphoblastic leukemic cells and the bone marrow stromal cell microenvironment.
Development of a model for evaluating the interaction between human pre-B acute lymphoblastic leukemic cells and the bone marrow stromal cell microenvironment.
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DOI：
10.1182/blood.v92.10.3817.422k12_3817_3828
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发表时间：
1998-11
期刊：
影响因子：
20.3
通讯作者：
Nisha Shah;L. Oseth;T. Lebien
中科院分区：
文献类型：
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作者：
Nisha Shah;L. Oseth;T. Lebien
b细胞前体急性淋巴细胞白血病（ALL）的克隆扩增可能受到骨髓（BM）微环境转导的生存、生长和死亡信号的调节。利用支持正常人b细胞前体生长的人骨髓基质细胞培养物，我们建立了一种b ALL前细胞系，命名为BLIN-2。BLIN-2具有Ig重链位点的克隆重排、dic（9;20）染色体异常以及p16（INK4a）和p19（ARF）基因的双等位基因缺失。BLIN-2最有趣的特征是它绝对依赖于贴壁的人骨髓基质细胞来维持生存和生长。在没有骨髓基质细胞的情况下培养的BLIN-2会发生凋亡，直接接触有活力的骨髓基质细胞是实现最佳生长的必要条件。BLIN-2细胞也生长在血管细胞粘附分子-1 （VCAM-1）阴性的人皮肤成纤维细胞上，这使得BLIN-2的生长不太可能需要非常晚的抗原-4 (vla4)/VCAM-1相互作用。Western blot分析在BM基质细胞存在或不存在的情况下培养的BLIN-2细胞表明，BLIN-2与BM基质细胞接触可诱导Rb过度磷酸化。相比之下，b前ALL细胞系BLIN-1具有p16(INK4a) p19（ARF）双等位基因缺失，但生长不需要BM基质细胞，在BM基质细胞接触后不发生Rb磷酸化。BLIN-2细胞系将有助于鉴定配体/受体在b细胞前体/BM间质细胞界面的相互作用，并可能为白血病细胞生存和生长的微环境调控提供新的见解。
Clonal expansion of B-cell precursor acute lymphoblastic leukemia (ALL) is potentially regulated by survival, growth, and death signals transduced by the bone marrow (BM) microenvironment. Using a human BM stromal cell culture that supports the growth of normal human B-cell precursors, we established a pre-B ALL cell line designated BLIN-2. BLIN-2 has a clonal rearrangement of the Ig heavy chain locus, a dic(9;20) chromosomal abnormality, and a bi-allelic deletion of the p16(INK4a) and p19(ARF) genes. The most interesting feature of BLIN-2 is an absolute dependence on adherent human BM stromal cells for sustained survival and growth. BLIN-2 cultured in the absence of BM stromal cells undergo apoptosis, and direct contact with viable BM stromal cells is essential for optimal growth. BLIN-2 cells also grow on vascular cell adhesion molecule-1 (VCAM-1)-negative human skin fibroblasts, making it unlikely that a very late antigen-4 (VLA-4)/VCAM-1 interaction is required for BLIN-2 growth. Western blot analysis of BLIN-2 cells cultured in the presence or absence of BM stromal cells demonstrates that contact of BLIN-2 with BM stromal cells induces hyperphosphorylation of Rb. In contrast, the pre-B ALL cell line BLIN-1, which has a bi-allelic deletion of p16(INK4a) p19(ARF) but does not require BM stromal cells for growth, does not undergo Rb phosphorylation after BM stromal cell contact. The BLIN-2 cell line will facilitate identification of ligand/receptor interactions at the B-cell precursor/BM stromal cell interface and may provide new insight into microenvironmental regulation of leukemic cell survival and growth.