Wrobel Tomasz, Pogrzeba Joanna, Stefanko Ewa, Wojtowicz Marcin, Jazwiec Bozena, Dzietczenia Justyna, Mazur Grzegorz, Kuliczkowski Kazimierz
Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, L. Pasteura 4 Street, 50-367, Wroclaw, Poland.
Pathol Oncol Res. 2014 Oct;20(4):901-7. doi: 10.1007/s12253-014-9767-9. Epub 2014 Apr 25.
Eph receptors represent the largest subfamily of receptor tyrosine kinases (RTKs). The up- regulation of Eph receptors has been documented in various solid tumors, where it often correlates with poor prognosis. Their significance in hematologic malignancies is still unclear. This study aimed to investigate the expression of Eph A4, Eph B2, and Eph B4 mRNA in non - M3 AML patients and determine their prognostic significance. Bone marrow samples from 101 newly diagnosed non - M3 AML patients and 26 healthy controls for comparison were quantified by real time reverse transcriptase polymerase chain reaction (RT-PCR), and the comparative cycle threshold (Ct) method was used to determine their relative expression levels to GUS control gene. The results showed that expression of all selected Eph receptors was significantly lower in AML patients comparing to controls. It also differed according to FAB subtypes. The decreased expression levels of Eph A4 were associated with higher leukocytes (p = 0.022) and blast cell counts (p = 0.001), and unfavorable FLT3-ITD mutation. Our study revealed significant correlation between lower EphB2 expression levels, and higher complete remission rate (p = 0.009724) and longer overall survival. Additionally, we found that patients with shorter RFS had decreased EphB4 expression (p = 0.00). In conclusion, the results suggest the prognostic impact of decreased expression levels of some Eph receptors in AML patients.
Eph受体是受体酪氨酸激酶(RTK)中最大的亚家族。Eph受体的上调在多种实体瘤中已有记载,在这些肿瘤中它常与不良预后相关。它们在血液系统恶性肿瘤中的意义仍不清楚。本研究旨在调查Eph A4、Eph B2和Eph B4 mRNA在非M3急性髓系白血病(AML)患者中的表达,并确定其预后意义。采用实时逆转录聚合酶链反应(RT-PCR)对101例新诊断的非M3 AML患者的骨髓样本以及26例作为对照的健康样本进行定量分析,并使用比较循环阈值(Ct)法确定它们相对于GUS对照基因的相对表达水平。结果显示,与对照组相比,所有选定的Eph受体在AML患者中的表达均显著降低。其表达也因FAB亚型而异。Eph A4表达水平降低与白细胞计数升高(p = 0.022)、原始细胞计数升高(p = 0.001)以及不良的FLT3-ITD突变相关。我们的研究揭示了EphB2表达水平较低与较高的完全缓解率(p = 0.009724)和较长的总生存期之间存在显著相关性。此外,我们发现无复发生存期较短的患者EphB4表达降低(p = 0.00)。总之,结果表明某些Eph受体表达水平降低对AML患者具有预后影响。