文章：

流式细胞术phospho-STAT5作为少年髓细胞白血病诊断工具的验证

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

原文发布日期：2013-11-15

DOI: 10.1038/bcj.2013.56

类型: Original Article

开放获取: 是

英文摘要：

To diagnose juvenile myelomonocytic leukemia (JMML) is sometimes challenging, because around 10% of patients lack molecular abnormalities affecting Ras-MAPK (mitogen-activated protein kinase) pathway and other diseases such as cytomegalovirus infection can mimic clinical signs of JMML. In order to validate a phospho-specific flow cytometry assay assessing phospho-signal transducer and activator of transcription factor 5 (p-STAT5) as a new diagnostic tool for JMML, we examined 22 samples from children with JMML and 47 controls. CD33+/CD34+ cells from 22 patients with JMML showed hyperphosphorylation of STAT5 induced by sub-saturating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a training set of samples (11 JMML and 23 controls), we identified a threshold for p-STAT5-positive after stimulation with 0.1 ng/ml GM-CSF (17.17%) that discriminates JMML from controls. This threshold was validated in an independent series (11 JMML, 24 controls and 7 cases with diseases other than JMML) where we demonstrated that patients with JMML could be distinguished from other subjects with a sensitivity of 91% (confidence interval (CI) 59–100%) and a specificity of 87% (CI 70–96%). Positive and negative predictive values were 71% (CI 42–92%) and 96% (CI 82–100%), respectively. In conclusion, flow cytometric p-STAT5 profiling is a reliable diagnostic tool for identifying patients with JMML and can contribute to consistency of current diagnostic criteria.

摘要翻译： 

诊断幼年型粒单核细胞白血病有时颇具挑战性，因为约10%的患者不存在影响Ras-MAPK（丝裂原活化蛋白激酶）信号通路的分子异常，且巨细胞病毒感染等其他疾病可能呈现与JMML相似的临床表现。为验证磷酸化特异性流式细胞术检测磷酸化信号转导与转录激活因子5可作为JMML新型诊断工具，我们检测了22例JMML患儿和47例对照者的样本。22例JMML患者的CD33+/CD34+细胞在亚饱和剂量粒细胞-巨噬细胞集落刺激因子刺激下呈现STAT5过度磷酸化。通过训练集样本（11例JMML和23例对照），我们确定了0.1纳克/毫升GM-CSF刺激后p-STAT5阳性阈值（17.17%），该阈值能有效区分JMML与对照组。在独立验证系列（11例JMML、24例对照及7例非JMML病例）中，该阈值得到验证：JMML患者与其他受试者的区分灵敏度达91%（置信区间59%-100%），特异度达87%（置信区间70%-96%），阳性预测值和阴性预测值分别为71%（置信区间42%-92%）和96%（置信区间82%-100%）。综上所述，流式细胞术p-STAT5分析是诊断JMML的可靠工具，有助于提升现有诊断标准的一致性。

原文链接：

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia