NFAT transcriptome in T-ALL

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 effects. NFAT
transcription factors play crucial roles downstream of calcineurin during
thymocyte development, T cell differentiation, activation and energy. 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.