Genotypic and functional diversity of phenotypically defined primitive hematopoietic cells in patients with chronic myeloid leukemia
Genotypic and functional diversity of phenotypically defined primitive hematopoietic cells in patients with chronic myeloid leukemia
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DOI：
10.1016/j.exphem.2013.07.001
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发表时间：
2013-10-01
影响因子：
2.6
通讯作者：
Eaves, Connie J.
中科院分区：
文献类型：
--
作者：
Sloma, Ivan;Beer, Philip A.;Eaves, Connie J.
在慢性期慢性粒细胞白血病（CP-CML）的管理方面已经取得了很大的进展，但仍然有必要开发治愈性治疗，预测患者对特定模式的反应，并预测疾病复发或进展。这些需求支撑了人们对以更高的可靠性和特异性检测和量化临床样本中相关白血病细胞的方法的持续兴趣。我们报告了比较三种方法在相同样品中计数原始CP-CML细胞的结果：通过荧光原位杂交直接对CD 34（+）38（-）细胞进行基因分型，并在含有非工程小鼠成纤维细胞的5周长期培养物（LTC）或含有经工程改造以产生人Steel因子的小鼠成纤维细胞的6周LTC中测量BCR-ABL 1转录基因分型集落形成细胞输出，粒细胞集落刺激因子和IL-3。结果表明，与第三种方法相比，前两种方法显着高估了原始CP-CML细胞的患病率。在另外的研究中，我们发现CML-CD 34（+）细胞可以在连续移植的成年NOD/SCID-IL-2 R γ链缺失小鼠的骨髓和脾脏中重新增殖超过1年，在原发和继发受体中几乎完全是髓样分化，并且没有疾病进展的证据。这些发现强调了长期功能性体外和体内终点对识别和表征CP-CML干细胞的重要性。皇冠版权所有（C）2013由Elsevier Inc.发布。代表ISEH -血液学和干细胞学会。All rights reserved.
Much progress has been made in the management of chronic-phase chronic myeloid leukemia (CP-CML), but there is a continuing imperative to develop curative treatments, predict patient responses to specific modalities, and anticipate disease relapse or progression. These needs underlie continuing interest in methods to detect and quantify the relevant leukemic cells in clinical samples with improved reliability and specificity. We report the results of comparing three methods to enumerate primitive CP-CML cells in the same samples: genotyping CD34(+)38(-) cells directly by fluorescence in situ hybridization, and measuring BCR-ABL1 transcript-genotyped colony-forming cell outputs in either 5-week long-term cultures (LTCs) containing non-engineered mouse fibroblasts or in 6-week LTCs containing mouse fibroblasts engineered to produce human Steel factor, granulocyte colony-stimulating factor, and IL-3. The results demonstrate that the first two methods significantly overestimate the prevalence of primitive CP-CML cells by comparison to the third. In additional studies, we found that CML-CD34(+) cells can repopulate the marrow and spleen of serially transplanted adult NOD/SCID-IL-2R gamma chain-null mice for more than 1 year with an almost exclusive myeloid differentiation in primary and secondary recipients and without evidence of disease progression. These findings underscore the importance of long-term functional in vitro and in vivo endpoints to identify and characterize CP-CML stem cells. Crown Copyright (C) 2013 Published by Elsevier Inc. on behalf of ISEH -Society for Hematology and Stem Cells. All rights reserved.