Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia.
Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia.
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DOI：
10.1038/bcj.2013.56
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发表时间：
2013-11-15
影响因子：
12.8
通讯作者：
Gaipa, G.
中科院分区：
文献类型：
--
作者：
Hasegawa, D.;Bugarin, C.;Giordan, M.;Bresolin, S.;Longoni, D.;Micalizzi, C.;Ramenghi, U.;Bertaina, A.;Basso, G.;Locatelli, F.;Biondi, A.;te Kronnie, G.;Gaipa, G.
诊断青少年粒单核细胞白血病（JMML）有时具有挑战性，因为约10%的患者缺乏影响Ras-MAPK（丝裂原活化蛋白激酶）通路的分子异常，并且其他疾病如巨细胞病毒感染可以模拟JMML的临床体征。为了验证磷酸特异性流式细胞术检测评估磷酸信号转导和转录激活因子5（p-STAT 5）作为一种新的诊断工具，为JMML，我们检查了22例样本与JMML和47名对照。来自22例JMML患者的CD 33 +/CD 34+细胞显示由亚饱和剂量的粒细胞-巨噬细胞集落刺激因子（GM-CSF）诱导的STAT 5过度磷酸化。使用样本的训练集（11个JMML和23个对照），我们确定了用0.1 ng/ml GM-CSF刺激后p-STAT 5阳性的阈值（17.17%），其区分JMML和对照。该阈值在一个独立的系列（11例JMML，24例对照和7例JMML以外的疾病）中得到验证，我们证明JMML患者可以与其他受试者区分开来，灵敏度为91%（置信区间（CI）59-100%），特异性为87%（CI 70-96%）。阳性和阴性预测值分别为71%（CI 42-92%）和96%（CI 82-100%）。总之，流式细胞术p-STAT 5分析是一种可靠的诊断工具，用于识别JMML患者，并有助于当前诊断标准的一致性。
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.
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影响因子：
20.3
作者：
Muramatsu, Hideki;Makishima, Hideki;Maciejewski, Jaroslaw P.
通讯作者：
Maciejewski, Jaroslaw P.
影响因子：
2.7
作者：
Nishio, Nobuhiro;Takahashi, Yoshiyuki;Kojima, Seiji
通讯作者：
Kojima, Seiji
DOI：
10.1097/01.mph.0000133599.34635.90
发表时间：
2004-09-01
影响因子：
1.2
作者：
Toyoda, H;Ido, M;Komada, Y
通讯作者：
Komada, Y
影响因子：
50.3
作者：
Kotecha N;Flores NJ;Irish JM;Simonds EF;Sakai DS;Archambeault S;Diaz-Flores E;Coram M;Shannon KM;Nolan GP;Loh ML
通讯作者：
Loh ML
影响因子：
78.5
作者：
Irish, JM;Kotecha, N;Nolan, GP
通讯作者：
Nolan, GP