Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates.
Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates.
复制标题
DOI：
10.1016/j.ccr.2008.08.014
复制
发表时间：
2008-10-07
期刊：
影响因子：
50.3
通讯作者：
Loh ML
中科院分区：
文献类型：
--
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
了解人脊髓增生性疾病（MPD）的分子发病机理的进展已导致诊断过程中纳入具有组织病理学的遗传测定法的指南。流式细胞仪的进步使得由于遗传病理而导致的细胞类型和信号传导异常成为可能。使用流式细胞仪，我们观察到了特定的诱发STAT5信号传导签名，该子集中的一部分来自涉嫌患有少年脊髓细胞性白血病（JMML）的患者，这是一种具有挑战性临床表现的侵略性MPD。该签名是涉及JAK-STAT信号传导的特定特征，这表明该途径在该疾病的生物学机制中起着关键作用，并指示了未来疗法的潜在靶标。
最近的进步已实现了使用流式细胞术同时测量主要种群中细胞类型和细胞信号的测量。该技术使一个问题：“我们可以通过信号传导从诊断到疾病进化的致癌细胞种群吗？”在使用特定抑制剂对关键信号转导途径的组成部分的时代，对于评估人类患者的治疗效果是必要的，并且随着癌细胞对这些治疗的反应改变其信号传导。这项工作使用这种方法随着时间的流逝跟随患者，并表明幼年脊髓细胞性白血病（JMML）的疾病状况 - 在诊断，缓解，复发和转化时 - 由具有异常信号传导曲线的细胞的子集表示。
Progress in understanding the molecular pathogenesis of human myeloproliferative disorders (MPDs) has led to guidelines incorporating genetic assays with histopathology during diagnosis. Advances in flow cytometry have made it possible to simultaneously measure cell type and signaling abnormalities arising as a consequence of genetic pathologies. Using flow cytometry, we observed a specific evoked STAT5 signaling signature in a subset of samples from patients suspected of having juvenile myelomonocytic leukemia (JMML), an aggressive MPD with a challenging clinical presentation during active disease. This signature was a specific feature involving JAK-STAT signaling, suggesting a critical role of this pathway in the biological mechanism of this disorder and indicating potential targets for future therapies. Recent advances have enabled simultaneous measurement of cell type and cell signals in primary populations using flow cytometry. This technique enables the question, "Can we track oncogenic cell populations from diagnosis through disease evolution via signaling?" Doing so in an era of using specific inhibitors against components of key signal transduction pathways will be necessary to assess treatment effects in human patients and adapt as cancer cells alter their signaling in response to these treatments. This work uses such an approach to follow patients over time and shows that disease status in juvenile myelomonocytic leukemia (JMML) -- at diagnosis, remission, relapse, and transformation -- is indicated by a subset of cells with an abnormal signaling profile.
登录
查看更多内容
分子对肿瘤细胞缺氧的反应。
影响因子：
37.3
作者：
Kunz, Manfred;Ibrahim, Saleh M
通讯作者：
Ibrahim, Saleh M
DOI：
10.1073/pnas.96.12.7065
发表时间：
1999-06-08
影响因子：
11.1
作者：
Ahmadian, MR;Zor, T;Scheffzek, K
通讯作者：
Scheffzek, K
影响因子：
5.1
作者：
BaderMeunier, B;Tchernia, G;Dommergues, JP
通讯作者：
Dommergues, JP
影响因子：
20.3
作者：
Kratz, CP;Niemeyer, CM;Loh, ML
通讯作者：
Loh, ML
影响因子：
20.3
作者：
Levine, RL;Loriaux, M;Deininger, MWN
通讯作者：
Deininger, MWN