Stroma-supported culture of childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome
Stroma-supported culture of childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome
复制标题
DOI：
10.1172/jci118474
复制
发表时间：
1996-02-01
影响因子：
15.9
通讯作者：
Campana, D
中科院分区：
文献类型：
--
作者：
Kumagai, MA;Manabe, A;Campana, D
我们开发了一种基质细胞培养系统，可以抑制b系急性淋巴细胞白血病病例中恶性细胞的凋亡。通过对细胞间质层培养后细胞恢复的多参数流式细胞术测量，我们评估了70例新诊断的b系急性淋巴细胞白血病的生长潜力，并将结果与单一化疗方案的治疗结果联系起来。培养7 d后恢复的白血病细胞数量范围为< 1%至292%（中位数为91%）。细胞从间质层恢复不良的基础似乎是淋巴细胞倾向于进行凋亡。在4年随访时，细胞恢复率高的患者无事件生存率为50+/-9% (SE)，细胞恢复率低的患者无事件生存率为94+/-6%（小于或等于91%；P = 0.0003）。白血病细胞培养后恢复的预后价值超过了所有其他已知高风险特征的估计，并且在与所有相互竞争的协变量进行调整后仍然是最显著的。因此，白血病细胞在骨髓源性间质层上的存活能力反映了疾病的侵袭性，是b系急性淋巴细胞白血病儿童治疗结果的一个强有力的、独立的预测指标。
We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings to treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50+/-9% (SE) among patients with higher cell recoveries (> 91%), and 94+/-6% among those with reduced cell recoveries (less than or equal to 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia.