Toll-like receptor 9 signaling in chronic lymphocytic leukemia cell lines

被引:0
作者
Meloni, Miriam [1 ]
Sana, Ilenia [1 ]
Mantione, Maria Elena [1 ]
Riba, Michela [2 ]
Muzio, Marta [1 ,3 ]
机构
[1] Hosp San Raffaele IRCCS, Div Expt Oncol, Cell Signaling Unit, Milan, Italy
[2] IRCCS San Raffaele Hosp, Ctr Om Sci, Milan, Italy
[3] Osped San Raffaele, Div Expt Oncol, Cell Signaling Unit, via Olgettina 60, Milan, Italy
关键词
cell line; chronic lymphocytic leukemia; CpG; NFKBIZ; Toll-like receptor 9; GENE-EXPRESSION; CLL CELLS; STIMULATION;
D O I
10.1002/2211-5463.13726
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2367 / 2374
页数:8
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