Functional toll-like receptors (TLRs) are expressed by a majority of primary human acute myeloid leukemia cells and inducibility of the TLR signaling pathway is associatedwith a more favorable phenotype
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Acute myeloid leukemia (AML) is a highlyheterogeneous disease withregardto 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 (n = 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 nucleophosmin 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.
CitationBruserud Ø, Brenner AK. Functional toll-like receptors (TLRs) are expressed by a majority of primary human acute myeloid leukemia cells and inducibility of the TLR signaling pathway is Associated with a more favorable phenotype. Cancers. 2019;11(7):973.
Copyright 2019 The Authors.