The Tumor Microenvironment-Dependent Transcription Factors AHR and HIF-1α Are Dispensable for Leukemogenesis in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia.
[en] Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in the elderly and is characterized by the accumulation of mature B lymphocytes in peripheral blood and primary lymphoid organs. In order to proliferate, leukemic cells are highly dependent on complex interactions with their microenvironment in proliferative niches. Not only soluble factors and BCR stimulation are important for their survival and proliferation, but also the activation of transcription factors through different signaling pathways. The aryl hydrocarbon receptor (AHR) and hypoxia-inducible factor (HIF)-1α are two transcription factors crucial for cancer development, whose activities are dependent on tumor microenvironment conditions, such as the presence of metabolites from the tryptophan pathway and hypoxia, respectively. In this study, we addressed the potential role of AHR and HIF-1α in chronic lymphocytic leukemia (CLL) development in vivo. To this end, we crossed the CLL mouse model Eµ-TCL1 with the corresponding transcription factor-conditional knock-out mice to delete one or both transcription factors in CD19+ B cells only. Despite AHR and HIF-1α being activated in CLL cells, deletion of either or both of them had no impact on CLL progression or survival in vivo, suggesting that these transcription factors are not crucial for leukemogenesis in CLL.
Disciplines :
Oncology
Author, co-author :
GONDER, Susanne ; University of Luxembourg ; Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg
Largeot, Anne ; Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg
Gargiulo, Ernesto ; Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg
Pierson, Sandrine; Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg
Fernandez Botana, Iria; Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg ; Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg
Pagano, Giulia; Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg ; Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg
PAGGETTI, Jerome ; University of Luxembourg ; Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg
MOUSSAY, Etienne ; University of Luxembourg ; Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg
External co-authors :
no
Language :
English
Title :
The Tumor Microenvironment-Dependent Transcription Factors AHR and HIF-1α Are Dispensable for Leukemogenesis in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia.
FNRS “Télévie” Fonds National de la Recherche Luxembourg
Funding text :
Funding: This work was supported by grants from FNRS “Télévie” to S.G., A.L., I.F.B. and G.P. (7.4502.19, 7.4503.19, 7.4529.19, 7.6518.20), from Fonds National de la Recherche Luxembourg to E.G., S.P., J.P, and E.M. (PRIDE15/10675146/CANBIO, C20/BM/14592342, and C20/BM/14582635).This work was supported by grants from FNRS ?T?l?vie? to S.G., A.L., I.F.B. and G.P. (7.4502.19, 7.4503.19, 7.4529.19, 7.6518.20), from Fonds National de la Recherche Luxembourg to E.G., S.P., J.P, and E.M. (PRIDE15/10675146/CANBIO, C20/BM/14592342, and C20/BM/14582635).We thank Carlo Croce and John Byrd (OSU, OH) for the kind gift of E?-TCL1 mouse.
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