Pluta Agnieszka, Robak Tadeusz, Cebula Barbara, Majchrzak Agata, Pluta Piotr, Brzozowski Kamil, Stępka Konrad, Szmigielska-Kapłon Anna, Grzybowska-Izydorczyk Olga, Czemerska Magdalena, Smolewski Piotr, Wierzbowska Agnieszka
Department of Hematology, Medical University of Lodz, Lodz, Poland.
Department of Experimental Hematology, Medical University of Lodz, Lodz, Poland.
Arch Med Sci. 2019 Nov 19;17(3):700-707. doi: 10.5114/aoms.2019.89918. eCollection 2021.
The misbalance between a family of inhibitor of apoptosis proteins (IAP), regulated by the nuclear factor kappa B (NF-κB) and their natural antagonist second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO) are important to biology of acute myeloid leukemia (AML).
The aim of the study was to assess NF-κB and Smac/DIABLO proteins expression in blasts of 109 newly diagnosed AML patients using the multicolor flow cytometry and evaluate their influence on AML patients outcome.
Expression of NF-κB and of Smac/DIABLO proteins were found in 95% and 98% of the patients, respectively. A negative correlation between Smac/DIABLO and NF-κB was observed. Age < 60 years old as well as higher Smac/DIABLO expression were associated with a higher probability of complete response achievement in the multivariate analysis. Longer overall survival (OS) in the univariate and multivariate analyses was influenced by age < 60 years old, a favorable or intermediate-risk karyotype and high Smac/DIABLO expression. Additionally, in the survival analysis of the subgroups, the patients aged < 60 years old, with high Smac/DIABLO expression, lower NF-κB expression and < 50% of bone marrow blasts who were treated with standard treatment had better OS.
Lower NF-κB and higher Smac/DIABLO expression may influence AML patients outcome.
由核因子κB（NF-κB）调控的凋亡抑制蛋白（IAP）家族与其天然拮抗剂第二线粒体衍生的半胱天冬酶激活剂/低pI直接IAP结合蛋白（Smac/DIABLO）之间的失衡对急性髓系白血病（AML）的生物学特性具有重要意义。
本研究旨在使用多色流式细胞术评估109例新诊断AML患者原始细胞中NF-κB和Smac/DIABLO蛋白的表达，并评估它们对AML患者预后的影响。
分别在95%和98%的患者中发现了NF-κB和Smac/DIABLO蛋白的表达。观察到Smac/DIABLO与NF-κB之间呈负相关。在多变量分析中，年龄<60岁以及较高的Smac/DIABLO表达与更高的完全缓解概率相关。在单变量和多变量分析中，年龄<60岁、有利或中等风险核型以及高Smac/DIABLO表达影响了更长的总生存期（OS）。此外，在亚组生存分析中，年龄<60岁、Smac/DIABLO表达高、NF-κB表达低且骨髓原始细胞<50%且接受标准治疗的患者具有更好的OS。
较低的NF-κB和较高的Smac/DIABLO表达可能影响AML患者的预后。
