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Toll‐like receptor 9 signaling in chronic lymphocytic leukemia cell lines
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Toll‐like receptor 9 signaling in chronic lymphocytic leukemia cell lines
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Journal Article
Toll‐like receptor 9 signaling in chronic lymphocytic leukemia cell lines
2023
Overview
Chronic lymphocytic leukemia (CLL) is a prototypic neoplasia in which malignant cells strongly depend on microenvironmental stimulations in the lymphoid tissues where they accumulate; leukemic cells are exposed to interaction with bystander and accessory cells, as well as inflammatory soluble mediators. Cell lines are frequently used to model the pathobiology of this disease; however, they do not always recapitulate leukemic cell growth and response to stimulation, and no data are available on Toll‐like receptors (TLR) signaling in CLL cell lines. To address this gap, we analyzed HG3, MEC2, and PCL12 cell lines, before and after CpG stimulation, by RNA‐sequencing followed by bioinformatic analyses and validation experiments. We identified NFKBIZ mRNA and the corresponding IkBz protein as robust markers of TLR9 activation in both MEC2 and PCL12, but not in HG3 cells. Next, we compared our current results with previous results obtained with primary CLL patient samples and were able to conclude that MEC2 is most similar to the patients' cells in terms of global responsiveness to TLR stimulation; in particular, MEC2 better resembles the samples of patients, as it is characterized by high expression levels of IkBz, but with a lower number of genes regulated. To model the pathobiology of TLR9 response in CLL cell lines, we analyzed the transcriptome of MEC2, PCL12, and HG3 after CpG stimulation. MEC2 best recapitulates the characteristics of primary CLL cells in terms of TLR9 signaling, IkBz expression, and global molecular fingerprint, pointing to this cell line as the most appropriate preclinical model to study TLR stimulation in CLL.
Publisher
John Wiley & Sons, Inc,Wiley
Subject
/ Cancer
/ Cells
/ Chronic lymphocytic leukemia
/ CpG
/ Genomics
/ Humans
/ Leukemia
/ Leukemia, Lymphocytic, Chronic, B-Cell - genetics
/ Leukemia, Lymphocytic, Chronic, B-Cell - metabolism
/ Leukemia, Lymphocytic, Chronic, B-Cell - pathology
/ mRNA
/ NFKBIZ
/ Software
/ Toll-Like Receptor 9 - genetics
/ Toll-Like Receptor 9 - metabolism
/ Toll-Like Receptors - genetics
