GEO DataSets

(Submitter supplied) We investigated the mechanism of action of the HDAC inhibitor Givinostat in JAK2V617F cells. We confirm that the drug inhibits colony formation and proliferation and induces apoptosis at doses 2-3 fold lower in JAK2V617F (HEL, UKE1 and SET2) compared to JAK2 wild type cell lines (K562, KU812, THP1 and KG1). By global gene expression analysis, we observed 293 common genes in HEL and UKE1 modulated at 6 hour by Givinostat (179 up and 114 down), of which 8/8 were validated by RTQ-PCR. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

12 Samples

Download data: CEL

(Submitter supplied) The JAK2 mutation V617F is detectable in a majority of patients with Ph-negative myeloproliferative neoplasms (MPN). Enforced expression of JAK2 V617F in mice induces myeloproliferation and bone marrow (BM) fibrosis suggesting a causal role for the JAK2 mutant in the pathogenesis of MPN. However, little is known about mechanisms and effector molecules contributing to JAK2 V617F-induced myeloproliferation and fibrosis. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

6 Samples

Download data: CEL

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

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL13112 GPL19057

64 Samples

Download data: TSV

(Submitter supplied) Comparison of mRNA expression profiles of LT-HSCs with or without mutations in JAK2 and Ezh2 by RNA sequencing. LT-HSC mRNA was extracted from six different transgenic mice (SclCre, SclCre;Ezh2+/-, SclCre;Ezh2-/-, SclCre; JAK2V617F, SclCre; JAK2V617F;Ezh2+/-, SclCre; JAK2V617F;Ezh2-/-) 10 weeks after tamoxifen injection. Our study represents the first detailed analysis of mRNA expression profile of LT-HSC with or without mutations in JAK2 and Ezh2 , with biologic replicates, generated by RNA-seq technology. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

35 Samples

Download data: TSV

(Submitter supplied) Comparison of mRNA expression profiles of MEPs with or without mutations in JAK2 and Ezh2 by RNA sequencing. MEPs mRNA was extracted from six different transgenic mice (SclCre, SclCre;Ezh2+/-, SclCre;Ezh2-/-, SclCre; JAK2V617F, SclCre; JAK2V617F;Ezh2+/-, SclCre; JAK2V617F;Ezh2-/-) 10 weeks after tamoxifen injection. Our study represents the first detailed analysis of mRNA expression profile of MEP with or without mutations in JAK2 and Ezh2 , with biologic replicates, generated by RNA-seq technology. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

29 Samples

Download data: TSV

(Submitter supplied) Transcriptional profiling of transformed Ba/F3 cells by myeloproliferative neoplasm-associated JAK2 V617F mutant comparing control Ba/F3 cells expressing wild type JAK2.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL5642

1 Sample

Download data: GPR

(Submitter supplied) We studied the in vitro and in vivo efficacy of the HDAC inhibitor Givinostat/ITF2357 in BCP-ALL with CRLF2 rearrangements. We used BCP-ALL CRLF2- rearranged MHH-CALL4 and MUTZ5 cell lines as well as blasts from CRLF2 rearranged BCP-ALL patients and patients’ derived xenograft samples. We conclude that Givinostat may represent a novel and effective tool, in combination with current chemotherapy, to treat this subsets of ALL with poor prognosis and chemotherapy-related toxicity.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

10 Samples

Download data: CEL

(Submitter supplied) The type I JAK inhibitor ruxolitinib is approved for therapy of MPN patients but evokes resistance with longer exposure. Several novel type I JAK inhibitors were studied and we show that they uniformly induce resistance via a shared mechanism of JAK family heterodimer formation.Here we studied the expression profiles of SET2 cell lines persistent to several different type I JAK inhibitors in comparison to naive SET2 cells or in comparison to SET2 cells with acute exposure to ruxolitinib.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17303

24 Samples

Download data: TXT

(Submitter supplied) We describe a critical role for Cdk6 in JAK2V617F+ MPN evolution. The absence of Cdk6 ameliorates clinical symptoms and prolongs survival of JAK2V617F fl/+ vav-Cre mice. The Cdk6 protein interferes with three hallmarks of disease: besides regulating malignant stem cell quiescence, it promotes NFkB signaling and contributes to cytokine production while inhibiting apoptosis. The treatment with palbociclib did not mirror these effects, showing that the functions of Cdk6 in MPN pathogenesis are largely kinase-independent.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

15 Samples

Download data: TXT

(Submitter supplied) Transcriptomics analysis was performed on FACS purified HSPC subsets from SclCre;V617F mice and WT mice bone marrow. The goal of this study is to identify the molecular signatures that are specific to the mutant JAK2 expressing HSPC subsets. We found that mutant JAK2 activation caused dysregulated expression of large numbers of genes in primitive HSPC subsets. Furthermore, this analysis revealed molecular identity and developmental proximity of HSC CD41+/- cells within the HSPC hierarchy.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

23 Samples

Download data: CSV

(Submitter supplied) Increased energy requirement and metabolic reprograming is a hallmark of cancer cells. We found that mouse models of myeloproliferative neoplasms (MPN) expressing mutant JAK2 displayed systemic metabolic changes including hypoglycemia and adipose atrophy. Modulation of nutrient availability modified MPN manifestations and survival. Hypoglycemia in MPN mice correlated with hyperactive erythropoiesis and was due to a combination of elevated glycolysis and increased oxidative phosphorylation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

9 Samples

Download data: TSV

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

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Expression profiling by array

Platforms:

GPL24676 GPL16686

49 Samples

Download data: CEL, CHP, TAR

(Submitter supplied) Chronic myeloproliferative neoplasms (MPNs) exhibit a propensity for transformation to secondary acute myeloid leukemia (sAML), for which the underlying mechanisms remain poorly understood, resulting in limited treatment options and dismal clinical outcomes. Here, we performed bulk transcriptome profiling accompanied by single cell RNA-sequencing on CD34+ stem/progenitor cells from serial patient samples obtained at the chronic MPN and sAML phases, identifying aberrantly increased expression of dual-specificity phosphatase 6 (DUSP6) underlying disease transformation. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

20 Samples

Download data: TSV

(Submitter supplied) Pre B cell leukemia homeobox 1 (Pbx1) regulates the balance between self-renewal and differentiation of hematopoietic stem cells, and maintains proto-oncogenic transcriptional pathways implicated in several tumors. Its aberrant expression was found in a subset of myeloproliferative neoplasms (MPN) patients bearing the JAK2V617F mutation. To investigate if Pbx1 contributes to MPN, and to explore its potential as therapeutic target, we generated a new mouse strain, that we called JP, by crossing a known JAK2V617F inducible knock-in MPN model with a Pbx1 conditional-ko. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

11 Samples

Download data: TSV

(Submitter supplied) Inactivation of Ybx1 results in RNA mis-splicing, retained intron enrichment and disruption of the transcriptional and post-translational control of extracellular signal-regulated kinase (ERK) signaling

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

6 Samples

Download data: BED, BW, TXT

(Submitter supplied) Measurement of DNA-binding of YBX1 in the HEL cell line (JAK2V617F mutated human cells)

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

3 Samples

Download data: BIGWIG, TXT

(Submitter supplied) Janus kinases (Jak) mediate cytokine, hormone and growth factor responses in hematopoietic cells. Jak2 is one of the most frequently mutated genes in the aging hematopoietic system and in hematopoietic cancers. Mutations in Jak constitutively activate downstream signaling and are drivers of myeloproliferative neoplasms (MPN). In clinical use, Jak-inhibitors have incomplete effects on overall disease burden of Jak2 mutated clones prompting us to investigate the mechanism underlying disease persistence. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

8 Samples

Download data: XLSX

(Submitter supplied) Purpose: Loss of functional β cell mass is an essential feature of type 2 diabetes and recent studies indicate that cell dedifferentiation can result in the loss of functional cell mass. However, the mechanism of cell dedifferentiation has not been elucidated due to the lack of appropriate animal model. Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

5 Samples

Download data: BW

(Submitter supplied) Purpose: Loss of functional β cell mass is an essential feature of type 2 diabetes and recent studies indicate that cell dedifferentiation can result in the loss of functional cell mass. However, the mechanism of cell dedifferentiation has not been elucidated due to the lack of appropriate animal model. Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

6 Samples

Download data: BW

(Submitter supplied) Purpose: Loss of functional β cell mass is an essential feature of type 2 diabetes and recent studies indicate that cell dedifferentiation can result in the loss of functional cell mass. However, the mechanism of cell dedifferentiation has not been elucidated due to the lack of appropriate animal model. Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

12 Samples

Download data: BW