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Leukemic IL‐17RB signaling regulates leukemic survival and chemoresistance
Author(s) -
Guo HeZhou,
Niu LiTing,
Qiang WanTing,
Chen Juan,
Wang Juan,
Yang Hui,
Zhang Wu,
Zhu Jiang,
Yu ShanHe
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900099r
Subject(s) - myeloid leukemia , cancer research , leukemia , bone marrow , gene silencing , signal transduction , mapk/erk pathway , receptor , apoptosis , biology , medicine , chemistry , immunology , microbiology and biotechnology , gene , genetics
ABSTRACT Secreted proteins provide crucial signals that have been implicated in the development of acute myeloid leukemia (AML) in the bone marrow microenvironment. Here we identify aberrant expressions of inflammatory IL‐17B and its receptor ( IL‐17RB ) in human and mouse mixed lineage leukemia–rearranged AML cells, which were further increased after exposure to chemotherapy. Interestingly, silencing of IL‐17B or IL‐17RB led to significant suppression of leukemic cell survival and disease progression in vivo . Moreover, the IL‐17B–IL‐17RB axis protected leukemic cells from chemotherapeutic agent–induced apoptotic effects. Mechanistic studies revealed that IL‐17B promoted AML cell survival by enhancing ERK, NF‐κB phosphorylation, and the expression of antiapoptotic protein B‐cell lymphoma 2, which were reversed by small‐molecule inhibitors. Thus, the inhibition of the IL‐17B–IL‐17RB axis may be a valid strategy to enhance sensitivity and therapeutic benefit of AML chemotherapy.—Guo, H.‐Z., Niu, L.‐T., Qiang, W.‐T., Chen, J., Wang, J., Yang, H., Zhang, W., Zhu, J., Yu, S.‐H. Leukemic IL‐17RB signaling regulates leukemic survival and chemoresistance. FASEB J. 33, 9565–9576 (2019). www.fasebj.org