2020
DOI: 10.3389/fcell.2020.00262
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A Dual TLR7/TLR9 Inhibitor HJ901 Inhibits ABC-DLBCL Expressing the MyD88 L265P Mutation

Abstract: Diffuse large B cell lymphoma (DLBCL) is associated with aggressive clinical cases and poor prognosis despite recent advances in disease treatment. In activated B-cell-like (ABC)-DLBCL, the most severe damaged signaling pathways converge to aberrantly activate the Toll-like receptor (TLR) 7/9/MyD88 pathways, leading to the avoidance of cell death and resistance to chemotherapy. A gain of function mutation in MyD88 (MyD88 L265P) enhanced the NF-κB and JAK-STAT signaling pathways and was associated with dysregul… Show more

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Cited by 6 publications
(6 citation statements)
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“…However, in DLBCL NETs promote the survival of malignant B cells via TLR9-dependent manner [ 82 ]. In line with this observation the TLR9 antagonist was shown to be effective in reducing the growth of B-cell lymphoma [ 83 ].…”
Section: Defects In Neutrophils’ Functions and Their Influence On Immune Response Development In Cll And Dlbclmentioning
confidence: 79%
“…However, in DLBCL NETs promote the survival of malignant B cells via TLR9-dependent manner [ 82 ]. In line with this observation the TLR9 antagonist was shown to be effective in reducing the growth of B-cell lymphoma [ 83 ].…”
Section: Defects In Neutrophils’ Functions and Their Influence On Immune Response Development In Cll And Dlbclmentioning
confidence: 79%
“…PI3K/AKT/mTOR pathway involved in crucial functions such as cellular proliferation, cell cycle regulation, and cell motility in DLBCL [ 21 ]. JAK-STAT signaling pathways were associated with pathogenesis of ABC-DLBCL [ 22 ]. DLBCL patients with the NOTCH1 mutations have worse PFS and OS [ 23 ].…”
Section: Discussionmentioning
confidence: 99%
“…The connection between enhanced TLR expression and hematopoietic malignancies indicates there are therapeutic benefits from TLR signaling repression. Various novel TLR pathway inhibitors emerge, such as HJ901 (TLR7/9 inhibitor) [ 107 ] and CA-4948 (IRAK4 inhibitor) [ 108 ]. They are becoming the therapeutic targets for the treatment of MDS, AML, ABC-DLBCL, and non-Hodgkin’s lymphoma, among other diseases.…”
Section: Toll-like Receptors and Hematologymentioning
confidence: 99%