GEO DataSets

(Submitter supplied) The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

43 Samples

Download data: CEL

(Submitter supplied) Lymphotoxin-mediated activation of the lymphotoxin-β receptor (LTβR) has been implicated in several physiological and pathological processes, including lymphoid organ development, T-cell maturation, and solid and hematopoietic malignancies. Its role in T-cell acute lymphoblastic leukemia (T-ALL) or other T-cell malignancies has remained however to be investigated. Here we show that the genes encoding lymphotoxin (LT)-α and LTβ were expressed in T-ALL patient samples, more abundantly in the TAL/LMO molecular subtype, and in the TEL-JAK2 mouse model of cortical/mature T-ALL. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

10 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL570 GPL6244

87 Samples

Download data: CEL

(Submitter supplied) The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

30 Samples

Download data: CEL

(Submitter supplied) The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

14 Samples

Download data: CEL

(Submitter supplied) Affymetrix Microarrays were used to analyse gene expression in aortas and circulating CD115+ cells of ApoE- and ApoE/Lymphotoxin beta receptor (LTbR)-double-deficent mice fed a Western diet from 8 to 12 weeks of age in order to identify regulated genes and pathways leading to reduced atherosclerosis in ApoE-/-/LTbR-/- mice compared to ApoE-/- littermate controls.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL16570

14 Samples

Download data: CEL

(Submitter supplied) T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer frequently associated with activating mutations in NOTCH1. Early studies identified NOTCH1 as an attractive therapeutic target for the treatment of T-ALL through the use of gamma-secretase inhibitors (GSIs). Here, we characterized the interaction between PF-03084014, a clinically-relevant GSI, and dexamethasone in preclinical models of glucocorticoid-resistant T-ALL. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

8 Samples

Download data: CEL, CHP

(Submitter supplied) Gamma-secretase inhibitors (GSIs), which block the activation of NOTCH receptors, are being tested in the treatment of T-cell acute lymphoblastic leukemia (T-ALL). Thus far, limited antileukemic cytotoxicity and severe gastrointestinal toxicity have restricted the clinical application of these targeted drugs. Here we show that combination therapy with GSIs plus glucocorticoids can improve the antileukemic effects of GSIs and reduce their gut toxicity in vivo. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL8321

8 Samples

Download data: CEL, CHP

(Submitter supplied) Glucocorticoids are an essential component of the treatment of lymphoid malignancies and resistance to glucocorticoid therapy constitutes a prominent clinical problem in relapsed and refractory lymphoblastic leukemias. Constitutively active NOTCH signaling is involved in the pathogenesis of over 50% of T-cell lymphoblastic leukemia (T-ALL) which harbor activating mutations in the NOTCH1 gene. Aberrant NOTCH1 signaling has been shown to protect normal thymocytes from glucocorticoid induced cell death. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL571

8 Samples

Download data: CEL, CHP

(Submitter supplied) The study uses RNA sequencing to profile AZD1208 resistant (AZDR) vs AZD1208 sensitive HSB-2 cells. PIM inhibitor treatment decreases leukemia burden in early T-cell precursor acute lymphoblastic leukemias (ETP-ALL) both in vitro and in vivo. However, prolonged treatment of ETP-ALL with PIM kinase inhibitors results in PIM inhibitor resistance. The analysis revealed that the HOXA9, mTOR, MYC, NF-B, and PI3K-AKT pathways were activated in PIM inhibitor resistant ETP-ALL

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

6 Samples

Download data: TXT

(Submitter supplied) NOT PROVIDED; REQUESTED

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

1 Sample

Download data: MTX, TSV

(Submitter supplied) Purpose: Identify new therapeutic pathways for T-cell acute lymphoblastic leukemia (T-ALL) therapy. Methods: KOPTK1 cells were grown in the presence of 2µM RZ-2994 vs DMSO, and cells collected at 24 and 72 hours of treatment. Three samples were collected per treatment condition per time point. RNA was extracted from cells with an RNeasy Kit (Qiagen). Results: RZ-2994 treatment of T-ALL cell lines resulted in changes pathways affecting cell cycle control, amino acid metabolism and gene sets associated with MYC changes. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

12 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platforms:

GPL20301 GPL20795

64 Samples

Download data: BW

(Submitter supplied) Semi-synthetic glucocorticoids are used to treat a broad range of medical conditions including inflammation, autoimmunity, and lymphoid malignancies. While a large component of these effects can be attributed to glucocorticoid-induced apoptosis of normal and malignant lymphocyte, the molecular basis for the lymphocyte-specific apoptosis remains unclear. Moreover, the mechanisms of glucocorticoid resistance in lymphoid malignancy are poorly defined, and remain a significant barrier to cure. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL20301

2 Samples

Download data: BW

(Submitter supplied) Semi-synthetic glucocorticoids are used to treat a broad range of medical conditions including inflammation, autoimmunity, and lymphoid malignancies. While a large component of these effects can be attributed to glucocorticoid-induced apoptosis of normal and malignant lymphocyte, the molecular basis for the lymphocyte-specific apoptosis remains unclear. Moreover, the mechanisms of glucocorticoid resistance in lymphoid malignancy are poorly defined, and remain a significant barrier to cure. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20795

12 Samples

Download data: BW

(Submitter supplied) Semi-synthetic glucocorticoids are used to treat a broad range of medical conditions including inflammation, autoimmunity, and lymphoid malignancies. While a large component of these effects can be attributed to glucocorticoid-induced apoptosis of normal and malignant lymphocyte, the molecular basis for the lymphocyte-specific apoptosis remains unclear. Moreover, the mechanisms of glucocorticoid resistance in lymphoid malignancy are poorly defined, and remain a significant barrier to cure. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL20795

30 Samples

Download data: BW

(Submitter supplied) Semi-synthetic glucocorticoids are used to treat a broad range of medical conditions including inflammation, autoimmunity, and lymphoid malignancies. While a large component of these effects can be attributed to glucocorticoid-induced apoptosis of normal and malignant lymphocyte, the molecular basis for the lymphocyte-specific apoptosis remains unclear. Moreover, the mechanisms of glucocorticoid resistance in lymphoid malignancy are poorly defined, and remain a significant barrier to cure. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL20301

20 Samples

Download data: BW

(Submitter supplied) Glucocorticoids (GCs) are a central component of therapy for patients with T-cell acute lymphoblastic leukemia (T-ALL) and while resistance to GCs is a strong negative prognostic indicator in T-ALL, mechanisms of GC resistance remain poorly understood. Using diagnostic samples from patients enrolled on the frontline Children’s Oncology Group (COG) T-ALL clinical trial AALL1231, we demonstrate that one-third of primary T-ALLs are resistant to GCs when cultured in the presence of interleukin-7 (IL7), a cytokine that is critical for normal T-cell function and that plays a well-established role in leukemogenesis. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

75 Samples

Download data: TSV

(Submitter supplied) Introduction. Glucocorticoids are critical drugs used to treat acute lymphoblastic leukemia, and response to glucocorticoids is highly predictive of outcome. Here we report a study evaluating the NOD/SCID xenograft mouse model to investigate glucocorticoid-induced gene expression. Methods. NOD/SCID mice were inoculated with ALL-3, a glucocorticoid-sensitive xenograft, and when highly engrafted were randomised to either dexamethasone 15mg/kg or vehicle control IP. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6884

26 Samples

Download data: TXT

(Submitter supplied) A subset of T-ALL/T-LBL patients is characterized by overexpression of the oncogenic Serine/Threonine kinase PIM1. Mechanisms for PIM1 overexpression are translocations involving the TCRb and PIM1 loci, JAK/STAT activating mutations and responsiveness to cytokinens in the tumor microenvironment, such as IL7. In this study, we generated a TLX3+ JAKwt/STATwt IL7 responsive T-ALL PDX model using NSG mice. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: TXT