NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia

Fernandes, Mónica T; Caroco, Lara S.; Pacheco-Leyva, Ivette; R. dos Santos, Nuno

http://hdl.handle.net/10400.1/14394

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Authors

Fernandes, Mónica T

Caroco, Lara S.

Pacheco-Leyva, Ivette

R. dos Santos, Nuno

Abstract(s)

Activation of the receptor activator of nuclear factor-kappa B (RANK) by its ligand (RANKL) is involved in both solid and hematological malignancies, including multiple myeloma, acute myeloid leukemia and B-cell leukemia. Although RANKL expression has been described in normal T cells, a potential role in T-cell leukemia remains undefined. Here, we used a model of immature T-cell leukemia/lymphoma, the TEL-JAK2 transgenic mice, to assess RANKL expression in leukemic cells and its regulatory mechanisms. We found that Rankl mRNA was significantly overexpressed in leukemic T cells when compared to wild-type thymocytes, their nonmalignant counterparts. Moreover, Rankl mRNA and RANKL surface expression in leukemic cells was induced by T-cell receptor (TCR) signaling activation, dependently on the NFKB signaling pathway. These results indicate that TCR-activated leukemic T cells express high levels of RANKL and are potential inducers of RANK signaling in microenvironmental cells. (C) 2019 Elsevier Inc. All rights reserved.