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Characterization of hemopoietic stem cells in chronic myeloid leukemia (CML).

机译：慢性粒细胞白血病（CML）中造血干细胞的特征。

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摘要

Much evidence indicates that the target of neoplastic transformation in chronic myeloid leukemia (CML) is a pluripotent hemopoietic stem cell, from which differentiated blood cells of the myeloid and lymphoid lineages are normally derived throughout adult life. CML is one of the best defined hematologic malignancies, being characterized by a consistent chromosomal and molecular abnormality, the Philadelphia (Ph;The proliferative/self-maintenance and differentiative capacities of CML LTC-IC were also studied. CML LTC-IC were not different from normal LTC-IC in terms of either the total number or different types of clonogenic cells they produced after 5 weeks. However, CML LTC-IC were defective in their self-maintenance. These results, together with the decreased quantity of these cells in CML marrow, explains why leukemic progenitor output rapidly declines in LTC initiated with CML marrow.;In summary, my thesis demonstrates that primitive CML hemopoietic cells can be detected, quantitated, and phenotypically and functionally characterized using the LTC-IC assay recently developed for normal marrow. The data obtained provide an explanation for the rapid and selective decline of CML progenitors observed in LTC initiated with CML marrow, but not CML blood. The phenotypic differences of leukemic and normal LTC-IC should provide important information for the design of new treatment strategies and for further studies into the pathogenetic mechanisms leading to the development of the neoplastic clone in CML.;Characterisation of LTC-IC and clonogenic cells in CML blood and their comparison to these cells in normal marrow and blood showed some similarities and differences. Most (but not all) CML clonogenic cells were similar to clonogenic cells in normal marrow, but different from clonogenic cells in normal blood in terms of their apparent activation state, as measured by Rh-123 staining, HLA-DR expression, forward light scatter, and sensitivity to 4-hydroperoxycyclophosphamide. Most but not all CML LTC-IC were also found to express an activated phenotype, and thus differed from the LTC-IC in normal marrow and blood which exhibit a phenotype expected of quiescent cells.
机译：许多证据表明，慢性粒细胞白血病（CML）的肿瘤转化靶标是多能造血干细胞，通常从成年个体中衍生出髓样和淋巴谱系的分化血细胞。 CML是定义最明确的血液系统恶性肿瘤之一，其特征是一致的染色体和分子异常，Philadelphia（Ph;还研究了CML LTC-IC的增殖/自我维持和分化能力。CMLLTC-IC没有区别在5周后产生的克隆细胞总数或不同类型方面，均与正常LTC-IC相比有所下降，但是CML LTC-IC的自我维护能力却有缺陷，这些结果以及这些细胞数量的减少CML骨髓，解释了为什么以CML骨髓启动的LTC中白血病祖细胞输出迅速下降的原因。总而言之，我的论文表明，使用最近针对正常人开发的LTC-IC分析，可以检测，定量和表型和功能表征原始CML造血细胞所获得的数据解释了在以CML骨髓引发的LTC中观察到的CML祖细胞的快速选择性下降，但并非如此CML血。白血病和正常LTC-IC的表型差异应为设计新的治疗策略和进一步研究导致CML肿瘤性克隆发展的致病机制提供重要信息。LTC-IC和克隆细胞的特征CML血液及其与正常骨髓和血液中这些细胞的比较显示出一些相似之处和不同之处。通过Rh-123染色，HLA-DR表达，前向光散射测量，大多数（但不是全部）CML克隆细胞与正常骨髓中的克隆细胞相似，但就其表观活化状态而言，与正常血液中的克隆细胞不同。 ，对4-氢过氧环磷酰胺敏感。还发现大多数（但不是全部）CML LTC-IC均表现出活化的表型，因此在正常骨髓和血液中表现出预期的静止细胞表型不同于LTC-IC。

著录项

  • 作者

    Udomsakdi, Chirayu.;

  • 作者单位

    The University of British Columbia (Canada).;

  • 授予单位 The University of British Columbia (Canada).;
  • 学科 Pathology.;Animal Physiology.;Immunology.;Cellular biology.
  • 学位 Ph.D.
  • 年度 1992
  • 页码 194 p.
  • 总页数 194
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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