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

Abstract Activation of the receptor activator of nuclear factor-κB (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 NF-κB 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.