NFAT transcriptome in T-ALL
Tran Quang, Christine; Passaro, Diana (2020), NFAT transcriptome in T-ALL, Dryad, Dataset, https://doi.org/10.5061/dryad.xd2547dfk
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.
3 independent tumor (#21, #23 and #24) having floxed alleles for NFAT2 and NFAT4 genes and NFAT1 knockout were injected into mice and treated with either OIL (O) or TAMOXIFEN (T) to induce gene recombination resulting in NFAT-proficient (O) or NFAT-deficient (T) leukemic cells. Resulting cells were collected from mice, RNA isolated and processed to be used on Affymetrix Mouse GeneChip® 430 2.0 arrays. Tumors #23 has been used twice independently.
JGL-21-O3 = tumor 21 OIL treated (NFAT-proficient)
JGL-21-T6= tumors 21 TAM-treated (NFAT-deficient)
JGL-23-O2 = tumor 23 OIL treated (NFAT-proficient)
JGL-23-T6= tumors 23 TAM-treated (NFAT-deficient)
JGL-23-O3 = tumor 23 OIL treated (NFAT-proficient)
JGL-23-T7= tumors 23 TAM-treated (NFAT-deficient)
JGL-24-O2 = tumor 21 OIL treated (NFAT-proficient)
JGL-24-T5= tumors 21 TAM-treated (NFAT-deficient)
MAS5 raw data are provided that have been analyzed using the software "Expression Console" and then saved as Excel files.
Raw data are the fluorescence intensity (AU).
Centre National de la Recherche Scientifique
Ligue Nationale Contre le Cancer