Project description:The development of a clinically relevant xenograft model of pediatric acute lymphoblastic leukemia, using a 4-drug treatment regimen designed to mimic pediatric remission induction therapy. Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. This study was designed to establish a preclinical model of resistance to induction therapy in childhood T-ALL to examine the emergence of drug resistance and identify novel therapies. We performed transcription profiling by array of human CD45-positive human lymphocytes from patients with acute pediatric lymphoblastic leukemia, and from xenografted NOD/SCID mice treated with vincristine, daunorubicin, dexamethasone and L-asparagine. Several different treatment regimes were used in this study (VLXD, VLXDR, VLXD2, VXL and VLXD2-ALL31) and are summarised in the protocols associated with this submission.
Project description:Proteogenomic analysis and genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of High hyperdiploid childhood acute lymphoblastic leukemia.
Project description:This SuperSeries is composed of the following subset Series: GSE24381: Inhibition of BCL6-dependent gene expression in Philadelphia chromosome positive acute lymphoblastic leukemia GSE24404: Recruitment of BCL6 to target genes in Philadelphia chromosome positive acute lymphoblastic leukemia Refer to individual Series
Project description:Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. Gene expression profiling of 64 T-ALL patient samples
Project description:This SuperSeries is composed of the following subset Series: GSE25102: Illumina SNP-array data for 2 ETV6/RUNX1-positive Acute Lymphoblastic Leukemia samples and corresponding normal samples GSE25116: Affymetrix SNP-array data for 2 ETV6/RUNX1-positive Acute Lymphoblastic Leukemia samples and corresponding normal samples Refer to individual Series
Project description:Proteogenomic analysis and genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of High hyperdiploid childhood acute lymphoblastic leukemia.
Project description:The goals of this study aim to reveal functional and phenotypic diversity of Spleenic Macrophage subpopulations identified by Ly6c and F4/80 in response to the microenvironmental cues in mouse T cell acute lymphoblastic leukemia
Project description:Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. The current study used a pre-clinical model of induction therapy for pediatric ALL in NOD/SCID mice (Samuels et al Blood Cancer Journal (2014) 4, e232; doi:10.1038/bcj.2014.52) to study the development of drug resistance. We performed transcription profiling by array of human CD45-positive lymphocytes from patients with acute pediatric lymphoblastic leukemia, xenografted in NOD/SCID mice treated with vincristine, daunorubicin, dexamethasone and L-asparagine. Both the primary-patient-derived and xenograft cells were analysed. The VLXD2 treatment regime is described in full in the protocols associated with this submission and in Samuels et al (Blood Cancer Journal (2014) 4, e232; doi:10.1038/bcj.2014.52). This study is an extension of E-MEXP-3916.
Project description:Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. Gene expression was measured in sorted T-cell subsets of 4 healthy donors.