Adhesion-dependent survival of normal and leukemic human B lymphoblasts on bone marrow stromal cells.
Adhesion-dependent survival of normal and leukemic human B lymphoblasts on bone marrow stromal cells.
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DOI：
10.1182/blood.v83.3.758.bloodjournal833758
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发表时间：
1994-02
期刊：
影响因子：
20.3
通讯作者：
A. Manabe;G. Murti;E. Coustan-Smith;M. Kumagai;F. Behm;S. Raimondi;D. Campana
中科院分区：
文献类型：
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作者：
A. Manabe;G. Murti;E. Coustan-Smith;M. Kumagai;F. Behm;S. Raimondi;D. Campana
我们调查了正常供者和白血病儿童的骨髓基质与B淋巴母细胞亲密接触的需求。在扫描电子显微镜下，种植在基质上的正常和白血病细胞都被基质细胞皱折包围，或由细长的卷须和尾足连接到基质上。使用微孔膜从基质中分离正常的B祖细胞，与接触畅通时的结果相比，细胞回收率显著降低。例如，直接在基质上培养7天后，CD19+、CD34+细胞(大多数未成熟亚群)的回收率为22.5%+/-1.8%(均值+/-扫描电子显微镜)，相比之下，在膜上生长后回收率为5.2%+/-0.7%(P<；.001经学生t检验)。在11例B系急性淋巴细胞性白血病中，6例分离祖细胞和基质导致细胞凋亡，细胞回收率下降60%以上。然而，在其余5例中，这种影响要明显得多，细胞恢复率从对照的48.5%到不到1%(中位数，39.0%)不等。抑制非常晚期抗原-4是B淋巴母细胞与基质黏附的关键表面分子，与同等的白血病细胞相比，正常CD34+B祖细胞的损失更大。这些结果建立了与基质的直接接触作为正常B淋巴母细胞的生存要求，并表明B系白血病细胞对基质的依赖具有明显的异质性。
We investigated the requirement for intimate contact between bone marrow stroma and B lymphoblasts from normal donors and children with leukemia. By scanning electron microscopy, both normal and leukemic cells seeded onto stroma were surrounded by folds of stromal cells or were linked to the stroma by fine tendrils and uropods. Separation of normal B progenitors from stroma by use of microporous membranes led to significantly lower cell recoveries compared with results when contact was unimpeded. For instance, 22.5% +/- 1.8% (mean +/- SEM) of CD19+, CD34+ cells (most immature subset) were recovered after a 7-day culture directly on stroma, compared with 5.2% +/- 0.7% after growth on membranes (P < .001 by Student's t test). In 6 of 11 cases of B-lineage acute lymphoblastic leukemia, separation of progenitors from stroma resulted in apoptosis and a greater than 60% reduction in cell recovery. In the remaining 5 cases, however, this effect was much less pronounced, with reductions in cell recoveries ranging from 48.5% to less than 1% (median, 39.0%) of control values. Inhibition of very late antigen-4, a surface molecule critical for adhesion of B lymphoblasts to stroma, was associated with a greater loss of normal CD34+ B progenitors compared with that for equivalent leukemic cells. These results establish direct contact with stroma as a survival requirement of normal B lymphoblasts and show marked heterogeneity in stromal dependency among B-lineage leukemic cells.