Division for Hematology, Institute of Clinical Science, University of Bergen, Bergen, Norway; Division for Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway; Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway.
Cell Prolif. 2013 Oct;46(5):554-62. doi: 10.1111/cpr.12057.
Proliferative capacity of acute myelogenous leukaemia (AML) blasts is important for leukaemogenesis, and we have investigated whether proliferative capacity of primary human AML cells could be used for subclassification of patients.
In vitro proliferative capacity of AML cells derived from two independent groups was investigated. Cells were cultured under highly standardized conditions and proliferation assayed by (3) H-thymidine incorporation after seven days culture. Patients were subclassified by clustering models, and gene expression profile was examined by microarray analyses.
Based on proliferative capacity of the AML cells, three different patient clusters were identified: (i) autocrine proliferation that was increased by exogenous cytokines; (ii) detectable proliferation only in presence of exogenous cytokines; and (iii) low or undetectable proliferation even in presence of exogenous cytokines. Patients with highest proliferative capacity cells had no favourable prognostic impact by NPM-1 mutation. Analysis of gene expression profiles showed that the most proliferative cells generally had altered expression of genes involved in regulation of transcription/RNA functions, whereas patients with high proliferative capacity and internal tandem duplications (ITDs) in the FLT3 cytokine receptor gene had altered expression of several molecules involved in cytoplasmic signal transduction.
In vitro proliferative capacity of primary human AML cells was considerably variable between patients and could be used to identify biologically distinct patient subsets.
急性髓系白血病（AML）白血病细胞的增殖能力对于白血病的发生非常重要，我们已经研究了能否将原发性人 AML 细胞的增殖能力用于患者的亚分类。
研究了两组独立的 AML 细胞的体外增殖能力。在高度标准化的条件下培养细胞，并在培养七天后通过（3）H-胸腺嘧啶掺入来测定增殖。通过聚类模型对患者进行分类，并通过微阵列分析检查基因表达谱。
基于 AML 细胞的增殖能力，确定了三个不同的患者群：（i）自分泌增殖，可被外源性细胞因子增强；（ii）仅在外源细胞因子存在时可检测到增殖；（iii）即使在外源细胞因子存在时，增殖也很低或无法检测到。具有最高增殖能力细胞的患者，NPM-1 突变并没有带来有利的预后影响。基因表达谱分析表明，最具增殖能力的细胞通常表现出与转录/RNA 功能调节相关的基因表达改变，而具有高增殖能力和 FLT3 细胞因子受体基因内串联重复（ITDs）的患者则表现出参与细胞质信号转导的几个分子的表达改变。
原发性人 AML 细胞的体外增殖能力在患者之间差异很大，可以用于识别生物学上不同的患者亚群。
