Prevalence and growth characteristics of malignant stem cells in B-lineage acute lymphoblastic leukemia

Prevalence and growth characteristics of malignant stem cells in B-lineage acute lymphoblastic leukemia
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DOI:
10.1182/blood.v89.10.3735.3735_3735_3744
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发表时间:
1997-05-15
期刊:
影响因子:
20.3
通讯作者:
Campana, D
Campana, D
中科院分区:
医学1区
文献类型:
--
作者:
Nishigaki, H;Ito, C;Campana, D

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我们采用基质支持培养的方法研究急性淋巴细胞白血病(ALL)中恶性干细胞的患病率和生长特性。在108例B系ALL样本中,51例骨髓来源的基质燕麦不仅抑制ALL细胞的凋亡,而且还支持它们在无血清培养基中的增殖。当将单个白血病细胞置于微量滴定板的基质包被的威尔斯孔中时,培养2至5个月后白血病细胞生长的威尔斯孔百分比范围为6%至20%(中位数,15%; 5次实验)。从这些培养物中回收的细胞的免疫表型和遗传特征与培养前记录的相同。所有细胞均保持其基质依赖性和自我更新能力。来自单个细胞的白血病克隆在培养1个月后含有约10(3)至10(6)个细胞;其他克隆仅在长时间培养后才可检测到。基质包被的威尔斯孔中的细胞生长与初始接种细胞的数量相关(1或10:r = 0.87)。然而,观察到的接种10个细胞的阳性威尔斯孔的百分比总是超过单细胞起始培养物结果的预测值(配对t检验P <0.003),表明旁分泌因子刺激白血病细胞生长。总之,具有克隆形成潜力的ALL细胞的比例可能比以前认为的要高得多。(C)1997年,美国血液学会。
We used a stroma-supported culture method to study the prevalence and growth characteristics of malignant stem cells in acute lymphoblastic leukemia (ALL). In 51 of 108 B-lineage ALL samples, bone marrow-derived stroma oat only inhibited apoptosis of ALL cells but also supported their proliferation in serum-free medium. When single leukemic cells were placed in the stroma-coated wells of microtiter plates, the percentage of wells with leukemic cell growth after 2 to 5 months of culture ranged from 6% to 20% (median, 15%; 5 experiments). The immunophenotypes and genetic features of cells recovered from these cultures were identical to those noted before culture. All cells maintained their stroma dependency and self-renewal capacity. Leukemic clones derived from single cells contained approximately 10(3) to 10(6) cells after 1 month of culture; other clones became detectable only after prolonged culture. Cell growth in stroma-coated wells correlated with the number of initially seeded cells (1 or 10: r = .87). However, the observed percentages of positive wells seeded with 10 cells always exceeded values predicted from results with single-cell-initiated cultures (P < .003 by paired t-test), suggesting stimulation of leukemic cell growth by paracrine factors. In conclusion, the proportion of ALL cells with clonogenic potential may be considerably higher than previously thought. (C) 1997 by The American Society of Hematology.