NFAT transcription factors are essential and redundant actors for leukemia initiating potential in T-cell acute lymphoblastic leukemia.
Claire CatherinetDiana PassaroStéphanie GachetHind MedyoufAnne ReynaudCharlène LasgiJacques GhysdaelChristine Tran QuangPublished in: PloS one (2021)
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few available targeted therapies. We previously reported that the phosphatase calcineurin (Cn) is required for LIC (leukemia Initiating Capacity) potential of T-ALL pointing to Cn as an interesting therapeutic target. Calcineurin inhibitors have however unwanted side effect. NFAT transcription factors play crucial roles downstream of calcineurin during thymocyte development, T cell differentiation, activation and anergy. Here we elucidate NFAT functional relevance in T-ALL. Using murine T-ALL models in which Nfat genes can be inactivated either singly or in combination, we show that NFATs are required for T-ALL LIC potential and essential to survival, proliferation and migration of T-ALL cells. We also demonstrate that Nfat genes are functionally redundant in T-ALL and identified a node of genes commonly deregulated upon Cn or NFAT inactivation, which may serve as future candidate targets for T-ALL.
Keyphrases
- acute lymphoblastic leukemia
- nuclear factor
- transcription factor
- genome wide identification
- genome wide
- lymph node metastasis
- acute myeloid leukemia
- bone marrow
- allogeneic hematopoietic stem cell transplantation
- induced apoptosis
- human health
- lymph node
- squamous cell carcinoma
- dna methylation
- oxidative stress
- current status
- cell proliferation
- gene expression
- signaling pathway
- free survival