Brenner Annette K, Bruserud Øystein
Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
Section for Hematology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.
Cancers (Basel). 2019 Jul 11;11(7):973. doi: 10.3390/cancers11070973.
Acute myeloid leukemia (AML) is a highly heterogeneous disease with regard to biological characteristics and receptor expression. Toll-like receptors (TLRs) are upstream to the transcription factor NFκB and part of the innate immune system. They are differentially expressed on AML blasts, and during normal hematopoiesis they initiate myeloid differentiation. In this study, we investigated the response upon TLR stimulation in an AML cohort ( = 83) by measuring the increase of NFκB-mediated cytokine secretion. We observed that TLR4 is readily induced in most patients, while TLR1/2 response was more restricted. General response to TLR stimulation correlated with presence of gene mutations, increased mRNA expression of proteins, which are part of the TLR signaling pathway and reduced expression of transcription-related proteins. Furthermore, signaling via TLR1/2 appeared to be linked with prolonged patient survival. In conclusion, response upon TLR stimulation, and especially TLR1/2 induction, seems to be part of a more favorable phenotype, which also is characterized by higher basal cytokine secretion and a more mature blast population.
急性髓系白血病（AML）在生物学特性和受体表达方面是一种高度异质性疾病。Toll样受体（TLR）位于转录因子NFκB的上游，是固有免疫系统的一部分。它们在AML原始细胞上差异表达，在正常造血过程中启动髓系分化。在本研究中，我们通过测量NFκB介导的细胞因子分泌增加，调查了一个AML队列（n = 83）中TLR刺激后的反应。我们观察到，大多数患者的TLR4很容易被诱导，而TLR1/2反应则更受限制。对TLR刺激的总体反应与基因突变的存在、作为TLR信号通路一部分的蛋白质的mRNA表达增加以及转录相关蛋白质的表达降低相关。此外，通过TLR1/2的信号传导似乎与患者生存期延长有关。总之，TLR刺激后的反应，尤其是TLR1/2的诱导，似乎是更有利表型的一部分，其特征还包括更高的基础细胞因子分泌和更成熟的原始细胞群体。
