Institute of Pathology, University of Basel, Schönbeinstrasse 40, 4031 Basel, Switzerland.
Ann Hematol. 2010 Jul;89(7):663-9. doi: 10.1007/s00277-009-0890-8. Epub 2010 Jan 12.
Mutations of the Fms-like tyrosine kinase 3 (FLT3) can be detected in a significant number of acute myeloid leukemias (AML). Seventy-five cases of acute myeloid leukemia were evaluated for FLT3-internal tandem duplications (ITD) by polymerase chain reaction. Paraffin-embedded formalin-fixed trephine biopsies of these cases were evaluated for expression of phosphorylated signal transducer and activator of transcription 1 (pSTAT1), pSTAT3, and pSTAT5. Specific expression of pSTAT5 was proven in leukemic blasts in situ by double staining with a blast-specific marker. Expression of pSTAT5 in > or =1% of blasts was highly predictive of FLT3-ITD. Neither expression of pSTAT1 nor pSTAT3 were associated with FLT3 mutations. Altogether we conclude that pSTAT5 expression can precisely be assessed by immunohistochemistry in routinely processed bone marrow trephines, STAT5 is highly likely the preferred second messenger of FLT3-mediated signaling in AML, and expression of pSTAT5 is predictive of FLT3-ITD.
Fms 样酪氨酸激酶 3（FLT3）的突变可在大量急性髓系白血病（AML）中检测到。通过聚合酶链反应（PCR）评估了 75 例急性髓系白血病患者的 FLT3 内部串联重复（ITD）。对这些病例的石蜡包埋甲醛固定活检进行磷酸化信号转导和转录激活因子 1（pSTAT1）、pSTAT3 和 pSTAT5 的表达评估。通过用白血病特异性标志物进行双重染色，原位证明了 pSTAT5 在白血病细胞中的特异性表达。白血病细胞中 pSTAT5 的表达大于等于 1%，可高度预测 FLT3-ITD。pSTAT1 和 pSTAT3 的表达均与 FLT3 突变无关。总之，我们得出结论，pSTAT5 的表达可以通过常规处理的骨髓活检中的免疫组织化学精确评估，STAT5 很可能是 AML 中 FLT3 介导的信号转导的首选第二信使，pSTAT5 的表达可预测 FLT3-ITD。
