Aberrant phosphorylation of STAT5 by granulocyte-macrophage colony-stimulating factor in infant cytomegalovirus infection mimicking juvenile myelomonocytic leukemia

Aberrant phosphorylation of STAT5 by granulocyte-macrophage colony-stimulating factor in infant cytomegalovirus infection mimicking juvenile myelomonocytic leukemia
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DOI:
10.1016/j.leukres.2011.04.014
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发表时间:
2011-09-01
期刊:
影响因子:
2.7
通讯作者:
Kojima, Seiji
Kojima, Seiji
中科院分区:
医学3区
文献类型:
--
作者:
Nishio, Nobuhiro;Takahashi, Yoshiyuki;Kojima, Seiji

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幼年粒单核细胞白血病(JMML)祖细胞对粒细胞-巨噬细胞集落刺激因子(GM-CSF)表现出体外超敏反应。磷酸化特异性流式细胞术是近年来报道的一种检测细胞GM-CSF超敏性的新方法。然而,使用甲基纤维素培养基测定GM-CSF超敏反应的菌落试验仍然是目前的金标准。有趣的是,婴儿期巨细胞病毒(CMV)感染经常表现出各种类似JMML的临床症状,CMV通过菌落试验得到阳性结果。我们想通过使用磷酸化特异性流式细胞术确定CMV感染中是否发生异常STAT 5激活,并确定该方法是否有效区分CMV感染和JMML。与正常个体的细胞相比,低剂量GM-CSF刺激后,JMML和CMV感染患者的外周血单核细胞中p-STAT 5细胞的比例升高。然而,我们发现在所使用的任何剂量的GM-CSF剂量下,CMV感染和JMML患者的p-STAT 5阳性细胞百分比均无显着差异。我们的结论是,CMV感染的患者不能与JMML患者区分这种新的诊断方法。(C)2011爱思唯尔有限公司保留所有权利。
Juvenile myelomonocytic leukemia (JMML) progenitor cells exhibit in vitro hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). Phospho-specific flow cytometry using anti-phosphorylated STAT5 antibody is a new method recently reported to detect GM-CSF hypersensitivity of cells. However, colony assays using methylcellulose medium to measure GM-CSF-hypersensitivity remain as the current gold standard. Interestingly, cytomegalovirus (CMV) infection in infancy often presents with a variety of clinical symptoms that mimic JMML, with CMV giving a positive result by colony assay. We wanted to determine whether aberrant STAT5 activation occurs in CMV infection by using phospho-specific flow cytometry, and to ascertain whether this method is effective at discriminating CMV infection from JMML. Peripheral blood mononuclear cells from patients with JMML and CMV infection displayed an elevated proportion of p-STAT5 cells after low-dose GM-CSF stimulation when compared with cells from normal individuals. However, we found no significant differences in the percentage of p-STAT5 positive cells from patients with CMV infection and JMML at any doses of the GM-CSF doses used. We conclude that patients with CMV infection cannot be discriminated from patients with JMML by this new diagnostic method. (C) 2011 Elsevier Ltd. All rights reserved.