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Proteomics and Drug Repurposing in CLL towards Precision Medicine
Article

The Tumor Microenvironment-Dependent Transcription Factors AHR and HIF-1α Are Dispensable for Leukemogenesis in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia

1
Tumor Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg
2
Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this paper as senior authors.
Academic Editor: Fabrice Gouilleux
Cancers 2021, 13(18), 4518; https://doi.org/10.3390/cancers13184518
Received: 20 August 2021 / Revised: 1 September 2021 / Accepted: 3 September 2021 / Published: 8 September 2021
(This article belongs to the Special Issue Novel Drug Targets and Advances in Treatment of CLL)
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, mostly affecting the elderly. The survival of leukemic cells depends on multiple soluble factors and on the stimulation of the BCR signaling pathway. Microenvironment-dependent transcription factors also contribute to CLL biology. Here, we generated new transgenic murine conditional knock-out models of CLL to study the role of the two transcription factors HIF-1α and AHR. Unexpectedly, we observed that both factors are dispensable for leukemia development in these models.
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. View Full-Text
Keywords: chronic lymphocytic leukemia; tumor microenvironment; AHR; HIF1α chronic lymphocytic leukemia; tumor microenvironment; AHR; HIF1α
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MDPI and ACS Style

Gonder, S.; Largeot, A.; Gargiulo, E.; Pierson, S.; Fernandez Botana, I.; Pagano, G.; Paggetti, J.; Moussay, E. The Tumor Microenvironment-Dependent Transcription Factors AHR and HIF-1α Are Dispensable for Leukemogenesis in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia. Cancers 2021, 13, 4518. https://doi.org/10.3390/cancers13184518

AMA Style

Gonder S, Largeot A, Gargiulo E, Pierson S, Fernandez Botana I, Pagano G, Paggetti J, Moussay E. The Tumor Microenvironment-Dependent Transcription Factors AHR and HIF-1α Are Dispensable for Leukemogenesis in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia. Cancers. 2021; 13(18):4518. https://doi.org/10.3390/cancers13184518

Chicago/Turabian Style

Gonder, Susanne, Anne Largeot, Ernesto Gargiulo, Sandrine Pierson, Iria Fernandez Botana, Giulia Pagano, Jerome Paggetti, and Etienne Moussay. 2021. "The Tumor Microenvironment-Dependent Transcription Factors AHR and HIF-1α Are Dispensable for Leukemogenesis in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia" Cancers 13, no. 18: 4518. https://doi.org/10.3390/cancers13184518

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