Dept. of Clinical Chemistry & Hematology, Zuyderland Medical Center, The Netherlands.
Nordic-MUbio, Susteren, The Netherlands.
Cytometry A. 2018 Nov;93(11):1097-1105. doi: 10.1002/cyto.a.23564. Epub 2018 Sep 3.
Because of the proven prognostic value of Ki-67 as a proliferation marker in several types of solid cancers, our goal is to develop and validate a multiparameter flow cytometric assay for the determination of the Ki-67 expression in hemato-oncological diseases. The aim of the present study was to establish the reference values for the fraction of Ki-67 positive cells in and during maturation of individual hematopoietic cell lineages present in normal bone marrow. Aspirates derived from femoral heads of 50 patients undergoing a hip replacement were used for the flow cytometric quantification of Ki-67 expression in the different hematopoietic cell populations of healthy bone marrow. Furthermore, the proliferative index was investigated in detail for the maturation steps during erythro-, myelo-, and monopoiesis using recently described immunophenotypic profiles in combination with a software-based maturation tool. Reference values for the proliferative index were established for different relevant hematopoietic cell populations in healthy bone marrow. During maturation, the size of the Ki-67 positive fraction was the highest in the most immature compartment of the myeloid, monocytic, and erythroid cell lineages, followed by a steady decline upon cell maturation. While proerythroblasts showed a proliferative activity of almost 100%, the myelo- and monoblast showed a lower proliferative index of on average of 50%, indicating that a relatively large proportion of these cells exist in a quiescent state. In conclusion, we can state that when using a novel combination of immunophenotypic markers, the proliferation marker (Ki-67) and a software-based maturation tool, it was possible to determine the proliferative fractions in the diverse hematopoietic cell lineages in bone marrow, in particular during maturation. Using this approach, the proliferative indices for the normal myelo-, mono-, and erythropoiesis were determined, which can be used as a reference in future studies of hematologic malignancies originating from bone marrow. © 2018 International Society for Advancement of Cytometry.
由于 Ki-67 作为多种实体瘤的增殖标志物具有明确的预后价值，我们的目标是开发和验证一种用于确定血液恶性肿瘤中 Ki-67 表达的多参数流式细胞术检测方法。本研究的目的是建立正常骨髓中单个造血细胞谱系成熟过程中 Ki-67 阳性细胞比例的参考值。从 50 例行髋关节置换术的患者的股骨头中抽吸骨髓，用于流式细胞术定量检测正常骨髓中不同造血细胞群体的 Ki-67 表达。此外，使用最近描述的免疫表型特征与基于软件的成熟工具，详细研究了红细胞生成、粒细胞生成和单核细胞生成过程中的增殖指数。为健康骨髓中不同相关造血细胞群体建立了增殖指数的参考值。在成熟过程中，Ki-67 阳性细胞的比例在髓系、单核细胞和红细胞谱系中最不成熟的细胞群中最高，随后细胞成熟时呈稳步下降。原红细胞表现出几乎 100%的增殖活性，而髓母细胞和单核母细胞表现出较低的增殖指数，平均为 50%，表明这些细胞中有相当大的比例处于静止状态。总之，当使用新型免疫表型标志物组合、增殖标志物（Ki-67）和基于软件的成熟工具时，可以确定骨髓中不同造血细胞谱系，特别是在成熟过程中的增殖分数。使用这种方法，可以确定正常髓系、单核系和红细胞生成的增殖指数，可作为未来源自骨髓的血液恶性肿瘤研究的参考。
© 2018 国际细胞分析协会。
