Cytogenetically aberrant cells in the stem cell compartment (CD34+lin-) in acute myeloid leukemia.
Cytogenetically aberrant cells in the stem cell compartment (CD34+lin-) in acute myeloid leukemia.
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DOI：
10.1182/blood.v86.3.1139.bloodjournal8631139
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发表时间：
1995-08
期刊：
影响因子：
20.3
通讯作者：
B. Mehrotra;T. George;K. Kavanau;H. Avet‐Loiseau;D. Moore;C. Willman;M. Slovak;S. Atwater;D. Head;M. Pallavicini
中科院分区：
文献类型：
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作者：
B. Mehrotra;T. George;K. Kavanau;H. Avet‐Loiseau;D. Moore;C. Willman;M. Slovak;S. Atwater;D. Head;M. Pallavicini
白血病可被视为原始细胞的克隆扩增;然而，原始细胞和/或干细胞在疾病病因和进展中的作用尚不清楚。我们研究了干细胞参与白血病使用荧光原位杂交（FISH），免疫荧光标记的造血细胞亚群，流式细胞仪分析/分选，以区分和定量细胞遗传学异常干细胞在12个急性髓性白血病（AML）和骨髓增生异常（MDS）标本。流式细胞术分析和分选用于区分和收集富含表达CD 34+和缺乏CD 33和CD 38（CD 34 +lin-）的干细胞的原始亚群。含有祖细胞和分化中的髓样细胞的亚群表达CD 34、CD 33和CD 38（CD 34 +lin+）。9份标本含有低于10%的CD 34+细胞，因此被认为是CD 34-白血病。成熟的淋巴细胞，骨髓细胞和红细胞亚群进行分类的基础上抗原联免疫荧光。在分选的亚群中，使用基于诊断核型选择的计数器探针的FISH鉴定细胞遗传学异常细胞。在所有标本中，细胞遗传学异常CD 34 +lin-细胞的频率在9%至99%之间。CD 34 +lin-细胞遗传学异常细胞占骨髓/血液标本的0.05%-11.9%。细胞遗传学异常的CD 34 +lin+细胞占骨髓/血液群体的0.01%至56%。这些数据表明，异常细胞存在于原始CD 34+干细胞区室中，甚至在CD 34-白血病中。干细胞参与进一步证实了淋巴和红细胞亚群从8个标本中，其中主要的白血病人群缺乏淋巴/红细胞分化标志物的排序。在这些样本以及多个谱系中，表明涉及具有多谱系能力的细胞。评价了异常CD 34 +lin-干细胞在免疫荧光确定的亚群中促进克隆和区室扩增的能力，以探索异常CD 34 +lin-细胞的功能表型。隔室大小和异常细胞频率的分析表明，细胞遗传学异常干细胞的频率与隔室大小无关。这些数据表明，原始隔室中的细胞遗传学异常细胞表现出不同的扩展原始隔室的能力。细胞遗传学异常的CD 34 +lin-细胞在分级成熟中先于原始细胞亚群，并且在某些情况下可能被认为是白血病前期，在转化（例如，房室扩增）发生之前需要成熟或额外突变。
Leukemia may be viewed as a clonal expansion of blast cells; however, the role of primitive cells and/or stem cells in disease etiology and progression is unclear. We investigated stem cell involvement in leukemia using fluorescence in situ hybridization (FISH), immunofluorescence labeling of hematopoietic subpopulations, and flow cytometric analysis/sorting to discriminate and quantify cytogenetically aberrant stem cells in 12 acute myeloid leukemia (AML) and three myelodysplastic (MDS) specimens. Flow cytometric analysis and sorting were used to discriminate and collect a primitive subpopulation enriched in stem cells expressing CD34+ and lacking CD33 and CD38 (CD34+lin-). A subpopulation containing progenitors and differentiating myeloid cells expressed CD34, CD33, and CD38 (CD34+lin+). Nine specimens contained less than 10% CD34+ cells and, thus, were considered to be CD34- leukemias. Mature lymphoid, myeloid, and erythroid subpopulations were sorted on the basis of antigen-linked immunofluorescence. Cytogenetically aberrant cells in sorted subpopulations were identified using FISH with enumerator probes selected on the basis of diagnosis karyotype. Cytogenetically aberrant CD34+lin- cells were present at frequencies between 9% and 99% in all specimens. CD34+lin- cytogenetically aberrant cells comprised between 0.05% and 11.9% of the marrow/blood specimens. Cytogenetically aberrant CD34+lin+ cells constituted 0.01% tp 56% of the marrow/blood population. These data demonstrate that aberrant cells are present in primitive CD34+ stem cell compartments, even in CD34- leukemias. Stem cell involvement was confirmed further by sorting lymphoid and erythroid subpopulations from eight specimens in which the predominant leukemic population lacked lymphoid/erythroid differentiation markers. In these specimens, as well as in multiple lineages, suggests involvement of a cell(s) with multilineage capabilities. The ability of aberrant CD34+lin- stem cells to contribute to clonal and compartment expansion within immunofluorescently defined subpopulations was evaluated to explore the functional phenotype of aberrant CD34+lin- cells. Analysis of compartment size and aberrant cell frequency suggests that frequency of cytogenetically aberrant stem cells is uncoupled from compartment size. These data suggest that cytogenetically aberrant cells in the primitive compartment show varying abilities to expand primitive compartments. Cytogenetically aberrant CD34+lin- cells precede the blast subpopulation in hierarchical maturation and may in some cases by considered preleukemic, requiring maturation or additional mutations before transformation (eg, compartmental expansion) occurs.