Detection of leukemic cells in the CD34+CD38- bone marrow progenitor population in children with acute lymphoblastic leukemia
Detection of leukemic cells in the CD34+CD38- bone marrow progenitor population in children with acute lymphoblastic leukemia
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DOI：
10.1182/blood.v97.12.3925
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发表时间：
2001-06-15
期刊：
影响因子：
20.3
通讯作者：
Weinberg, K
中科院分区：
文献类型：
--
作者：
George, AA;Franklin, J;Weinberg, K
儿童急性淋巴细胞白血病（ALL）中成功的自体造血干细胞（HSC）移植需要选择性地杀死白血病细胞或将正常HSC与白血病HSC分离的能力。基于先前的研究显示超过95%的儿童B系ALL表达CD 38，本研究评估了是否可以通过流式细胞术从患有B系ALL的儿童中分离出正常的CD 34（+）CD 38（-）祖细胞。在治疗第28天，即临床缓解时，从10名B系ALL儿童的骨髓样本中分离CD 34（+）细胞。将CD 34（+）祖细胞流式细胞术分选为CD 34（+）CD 38（+）和CD 34（+）CD 38（-）群体。可分离的CD 34（+）CD 38（-）细胞的绝对数量范围为401至6245。然后分析细胞中T细胞受体（TCR）V δ 2-D δ 3基因座的克隆型重排的存在。本研究仅纳入诊断性骨髓有信息性TCR V δ 2-D δ 3重排的患者。正常骨髓中的检测阈值通常为10（-4）至10（-5）个白血病细胞。在分析的10个样品中的6个中，分选的CD 34 + CD 38-细胞没有可检测的V δ 2-D δ 3重排。在4例病例中，在CD 34 + CD 38-群体中检测到克隆型白血病V delta 2-V delta 3重排，表明推定的正常HSC群体也含有白血病细胞。数据表明，尽管大多数儿童ALL细胞表达CD 34和CD 38，但白血病细胞也经常存在于CD 34（+）CD 38（-）群体中。因此，从ALL患儿中分离和移植正常HSC的策略将需要比CD 34（+）CD 38（-）表型更严格的正常HSC定义。
Successful autologous hematopoietic stem cell (HSC) transplantation in childhood acute lymphoblastic leukemia (ALL) requires the ability to either selectively kill the leukemia cells or separate normal from leukemic HSC, Based on previous studies showing that more than 95% of childhood B-lineage ALL express CD38, this study evaluated whether normal CD34(+)CD38(-) progenitors from children with B-lineage ALL could be isolated by flow cytometry. CD34(+) cells from bone marrow samples from 10 children with B-lineage ALL were isolated at day 28 of treatment, when clinical remission had been attained. The CD34(+) progenitor cells were flow cytometrically sorted into CD34(+)CD38(+) and CD34(+)CD38(-) populations. The absolute numbers of CD34(+)CD38(-) cells that could be isolated ranged from 401 to 6245, The cells were then analyzed for the presence of clonotypic rearrangements of the T-cell receptor (TCR) V delta2-D delta3 locus. Only patients whose diagnostic marrow had an informative TCR V delta2-D delta3 rearrangement were included in this study. Detection thresholds were typically 10(-4) to 10(-5) leukemic cells in normal marrow. In 6 of 10 samples analyzed, the sorted CD34+CD38- cells had no detectable V delta2-D delta3 rearrangements. In 4 cases, the clonotypic leukemic V delta2-V delta3 rearrangement was detected in the CD34+CD38- population, indicating that the putative normal HSC population also contained leukemic cells, The data indicate that although most childhood ALL cells express CD34 and CD38, leukemic cells are also frequently present in the CD34(+)CD38(-) population. Therefore, strategies to isolate and transplant normal HSC from children with ALL will require a more stringent definition of the normal HSC than the CD34(+)CD38(-) phenotype.