Characterization of acute lymphoblastic leukemia progenitor cells
Characterization of acute lymphoblastic leukemia progenitor cells
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DOI：
10.1182/blood-2004-03-0901
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发表时间：
2004-11-01
期刊：
影响因子：
20.3
通讯作者：
Blair, A
中科院分区：
文献类型：
--
作者：
Cox, CV;Evely, RS;Blair, A
据认为只有一些急性淋巴细胞白血病（ALL）细胞能够增殖以维持白血病克隆，并且这些细胞可能是治疗方案最相关的靶向细胞。我们开发了一种无血清悬浮培养（SC）系统，该系统支持33名患者的B - ALL细胞生长长达6周。28例（85%）患者的ALL细胞在该系统中扩增，并且在悬浮培养中的生长优于长期骨髓培养。为了表征ALL祖细胞，对细胞进行CD34和CD10或CD19表达的分选，并在悬浮培养和非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠中对亚群进行检测。能够在体外长期增殖和在NOD/SCID小鼠中重建种群的细胞仅来自CD34（+）/CD10（ - ）和CD34（+）/CD19（ - ）亚群，并且这些细胞能够植入二次受体。植入的细胞具有与诊断时相同的免疫表型和核型，表明它们在体内已分化。这些结果表明，能够在体外和体内长期增殖的ALL细胞是CD34（+）/CD10（ - ）/CD19（ - ）。这表明具有更不成熟表型的细胞，而非定向的B淋巴细胞，可能是B - ALL转化的靶点。（C）2004年美国血液学会版权所有。
Only some acute lymphoblastic leukemia (ALL) cells are thought to be capable of proliferating to maintain the leukemic clone, and these cells may be the most relevant to target with treatment regimens. We have developed a serum-free suspension culture (SC) system that supported growth of B-ALL cells from 33 patients for up to 6 weeks. ALL cells from 28 cases (85%) were expanded in this system, and growth was superior in SC than in long-term bone marrow culture. To characterize ALL progenitors, cells were sorted for expression of CD34 and CD10 or CD19 and the subfractions assayed in SC and in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Cells capable of long-term proliferation in vitro and NOD/SCID re-population were derived only from the CD34(+)/CD10(-) and CD34(+)/CD19(-) subfractions, and these cells could engraft secondary recipients. The engrafted cells had the same immunophenotype and karyotype as was seen at diagnosis, suggesting they had differentiated in vivo. These results demonstrate that ALL cells capable of long-term proliferation in vitro and in vivo are CD34(+)/CD10(-)/CD19(-). This suggests that cells with a more immature phenotype, rather than committed B-lymphoid cells, may be the targets for transformation in B-ALL. (C) 2004 by The American Society of Hematology.