We identify perhexiline, a small molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1 induced leukemias in vitro and in vivo. RNA-Seq from CUTLL1 cell lines treated with Perhexiline or vehicle for 3...
To formally address the biological activity of Hes1 in vivo, we tested the interaction between oncogenic NOTCH1 and acute Hes1 loss in a retroviral-transduction bone marrow transplantation model of NOTCH-induced T-ALL Forced expression of activated NOTCH1 in this model typically results in full leuk...
To formally address the biological activity of HES1 in vitro, we measured the transcriptional effect of HES1 inactivation infectiing CUTLL1 leukemia cell lines with shHES1 HES1 knockdown triggered apoptosis in human T-ALL lymphoblasts. We show that HES1 inactivation induces programmed cell death in ...
To analyze the prognostic relevance of transcriptional profiling in adult T-ALL, we analyzed a clinical series of 53 primary leukemia samples uniformly treated according to the ECOG E2993 protocol using gene expression oligonucleotide microarrays. Unsupervised analysis and consensus clustering of mi...
To formally address the tumor suppressor activity of Sh2b3 in vivo, we tested the interaction between oncogenic NOTCH1 and Sh2b3 loss in a retroviral- transduction bone marrow transplantation model of NOTCH-induced T-ALL Forced expression of activated NOTCH1 in this model typically results in full l...
Early immature T-cell acute lymphoblastic leukemias (T-ALLs) account for about 5-10% of pediatric T-ALLs and are associated with poor prognosis. However, the genetic defects that drive the biology of these tumors remain largely unknown. Analysis of microarray gene expression signatures in adult T-AL...
miRNA expression data for the "MicroRNA expression profiles classify human cancers". Keywords = miRNA Keywords = microRNA Keywords = normal Keywords = tumor Keywords = cell-line Keywords = cancer Keywords: other
Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors (GSI), which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been temper...
RNASeq sequencing.
Each library was sequenced using TruSeq SBS Kit v3-HS, in paired-end mode with a read length of 2 × 76 bp. We generated more than 20 million paired-end reads for each sample in a fraction of a sequencing lane on HiSeq2000 (Illumina Inc.) following the manufacturer’s protoc...
Chronic lymphocytic leukaemia (CLL) is a frequent and heterogeneous disease whose genetic alterations determining the clinicobiological behaviour are not fully understood. Here, we describe a comprehensive evaluation of the genomic landscape of 452 CLLs and 54 monoclonal B-lymphocytosis (MBL), a pre...
