Subclassification of patients with acute myelogenous leukemia based on chemokine responsiveness and constitutive chemokine release by their leukemic cells
Subclassification of patients with acute myelogenous leukemia based on chemokine responsiveness and constitutive chemokine release by their leukemic cells
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DOI：
10.3324/haematol.10148
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发表时间：
2007-03-01
期刊：
影响因子：
10.1
通讯作者：
Gjertsen, Bjorn Tore
中科院分区：
文献类型：
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作者：
Bruserud, Oystein;Ryningen, Anita;Gjertsen, Bjorn Tore
背景与目的趋化因子是一种可溶性介质，参与血管生成、细胞生长控制和免疫调节。在本研究中，我们研究了各种趋化因子对急性髓性白血病（AML）细胞增殖和原代AML细胞组成性趋化因子释放的影响。设计和方法体外培养来自68名连续患者的天然人AML细胞。我们研究了AML细胞增殖（H-3-胸苷掺入，集落形成），趋化因子受体表达，组成型趋化因子释放和正常外周血单核细胞的趋化性。但当研究生长因子依赖性（白细胞介素3 +粒细胞-巨噬细胞集落刺激因子+干细胞因子）悬浮培养物中的增殖鉴定了以下患者亚群：（i）其细胞显示趋化因子诱导的生长增强的患者（8名患者）;（ii）对增殖的不同影响（15名患者）;和（iii）无影响（大多数患者）。这些患者亚群在趋化因子受体表达方面没有差异，但是，与CD 34（-）AML细胞相比，CD 34（+）细胞显示出几种受体的更高表达。趋化因子还增加了来自第一亚组患者的克隆原性AML细胞的增殖。此外，在大多数患者中检测到广泛的组成型趋化因子释放曲线，并且可以鉴定出以下趋化因子簇：CCL 2 -4/CXCL 1/8、CCL 5/CXCL 9 -11（也可能是CCL 23）和CCL 13/17/22/24/CXCL 5（也可能是CXCL 6）。只有CCL 2 -4/CXCL 1/8簇显示相应的mRNA水平与NF κ B水平/活化之间存在显著相关性。正常免疫活性细胞的趋化性患者没有组成性趋化因子释放被观察到decreased.Interpretation和ConclusionsDifferences在趋化因子的反应，以及趋化因子释放有助于患者的异质性在AML。AML患者可根据其趋化因子反应性和趋化因子释放特征分为不同的亚组。
Background and ObjectivesChemokines are soluble mediators involved in angiogenesis, cellular growth control and immunomodulation. In the present study we investigated the effects of various chemokines on proliferation of acute myelogenous leukemia (AML) cells and constitutive chemokine release by primary AML cells.Design and MethodsNative human AML cells derived from 68 consecutive patients were cultured in vitro. We investigated AML cell proliferation (H-3-thymidine incorporation, colony formation), chemokine receptor expression, constitutive chemokine release and chemotaxis of normal peripheral blood mononuclear cells.ResultsExogenous chemokines usually did not have any effect on AML blast proliferation in the absence of hematopoietic growth factors, but when investigating growth factor-dependent (interleukin 3 + granulocyte-macrophage colony-stimulating factor + stem cell factor) proliferation in suspension cultures the following patient subsets were identified: (i) patients whose cells showed chemokine-induced growth enhancement (8 patients); (ii) divergent effects on proliferation (15 patients); and (iii) no effect (most patients). These patient subsets did not differ in chemokine receptor expression, but, compared to CD34(-) AML cells, CD34(+) cells showed higher expression of several receptors. Chemokines also increased the proliferation of clonogenic AML cells from the first subset of patients. Furthermore, a broad constitutive chemokine release profile was detected for most patients, and the following chemokine clusters could be identified: CCL2-4/CXCL1/8, CCL5/CXCL9-11 (possibly also CCL23) and CCL13/17/22/24/CXCL5 (possibly also CXCL6). Only the CCL2-4/CXCL1/8 cluster showed significant correlations between corresponding mRNA levels and NF kappa B levels/activation. The chemotaxis of normal immunocompetent cells for patients without constitutive chemokine release was observed to be decreased.Interpretation and ConclusionsDifferences in chemokine responsiveness as well as chemokine release contribute to patient heterogeneity in AML. Patients with AML can be classified into distinct subsets according to their chemokine responsiveness and chemokine release profile.