Chronic lymphocytic leukemia (CLL) is a disorder of mature B cells. Most patients are characterized by indolent disease and an anergic phenotype of their leukemia cells which refers to a state of unresponsiveness to B cell receptor stimulation. Using the E-TCL1 mouse model, we show that B cell-specific ablation of NFAT2 leads to the loss of the anergic phenotype culminating in a significantly compromised life expectancy and histological transformation to aggressive disease. We further define a gene expression signature of anergic CLL cells consisting of several NFAT2-dependant genes employing microarray technology.
NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia.
Age, Specimen part
View SamplesLipodystrophies resemble syndromes of disturbed adipocyte biology or development and severe congenital forms (CGL) lack adipose tissue. The ubiquitous immediate-early gene c-fos is one essential transcription factor to initiate adipocyte differentiation. In a CGL patient we identified a single homozygous point mutation in the promoter of c-fos gene. The mutation facilitates the formation of a novel specific protein/ DNA complex and ubiquitously reduces basal and inducible c-fos transcription activity.
A mutation in the c-fos gene associated with congenital generalized lipodystrophy.
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View SamplesSequencing libraries were generated from total RNA samples following the mRNAseq protocol for the generation of single end (16-36 hpf, 5 day larvae, adult head and adult tail) or paired end (24 hpf) libraries (Illumina). Single end reads of 36 nucleotides and paired end reads (2 x 76 nucleotides) were obtained with a GAIIx (Illumina). Gene expression at the different stages/tissu was assessed by cufflinks and HTseq. Overall design: RNAseq on 5 differents samples: 24hpf embryos, pool of 16 hour to 36 hour embryos, 5 days old larvea, adult head and adult tail
Genome-wide, whole mount in situ analysis of transcriptional regulators in zebrafish embryos.
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