GEO DataSets

(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:

GPL19057 GPL13112

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) 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) 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) 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) Pegylated interferon alpha (pegIFNα) can induce molecular remissions in JAK2-V617F-positive myeloproliferative neoplasms (MPN) patients by targeting long-term hematopoietic stem cells (LT-HSCs). Additional somatic mutations in genes regulating LT-HSC self-renewal, such as DNMT3A, have been reported to have poorer responses to pegIFNα. We investigated if DNMT3A loss leads to alterations in JAK2-V617F LT-HSCs functions conferring resistance to pegIFNα treatment in a mouse model of MPN and in hematopoietic progenitors from MPN patients. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

31 Samples

Download data: TSV

(Submitter supplied) We investigated if Dnmt3a loss leads to alterations in JAK2 V617F LT-HSCs heterogenity and expression profile using single-cell RNA sequencing.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

16 Samples

Download data: FA, GTF, TSV, TXT

(Submitter supplied) In this dataset, we determine the global gene expression in human induced pluripotent stem (iPS) cell-derived CD61+ megakaryocytes carrying homozygous JAK2 V617F mutation or the JAK2 wildtype gene.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: CSV

(Submitter supplied) The JAK2V617F mutation has been detected in ~50% cases of MF. Elevated expression of high mobility group AT hook 2 (HMGA2) also has been frequently observed in patients with MF. Interestingly, upregulation of HMGA2 expression has been found in association with the JAK2V617F mutation in significant cases of MF. However, the contribution of HMGA2 in the pathogenesis of MF remains elusive. To determine the effects of concurrent expression of HMGA2 and JAK2V617F mutation in hematopoiesis, we transduced bone marrow cells from Jak2V617F knock-in mice with lentivirus expressing Hmga2 and performed bone marrow transplantation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

6 Samples

Download data: TXT

(Submitter supplied) We report a Jak2V617F knock-in mouse myeloproliferative neoplasm (MPN) model resembling human polycythemia vera (PV). The MPN is serially transplantable and we demonstrate that the hematopoietic stem cell (HSC) compartment has the unique capacity for disease initiation but does not have a selective competitive advantage over wild type HSCs. In contrast, myeloid progenitor populations are expanded and skewed towards the erythroid lineage, but cannot transplant the disease. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

8 Samples

Download data: CEL

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

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL10787

12 Samples

Download data: TXT

(Submitter supplied) Loss-of-function mutations in EZH2 are associated with worse outcomes in patients with primary myelofibrosis (PMF). To understand how EZH2 insufficiency is involved in the pathogenesis of PMF, we generated mice compound for Ezh2 conditional deletion and a JAK2V617F transgene.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL10787

4 Samples

Download data: TXT

(Submitter supplied) Loss-of-function mutations in EZH2 are associated with worse outcomes in patients with primary myelofibrosis (PMF). To understand how EZH2 insufficiency is involved in the pathogenesis of PMF, we generated mice compound for Ezh2 conditional deletion and a JAK2V617F transgene.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL10787

8 Samples

Download data: TXT

(Submitter supplied) Interferon alpha (IFNa) is an effective treatment for patients with myeloproliferative neoplasms (MPN). In addition to inducing hematological responses in most MPN patients, IFNa reduces the JAK2V617F allelic burden and can render the JAK2V617F mutant clone undetectable in some patients. The precise mechanism underlying these responses is incompletely understood and whether the molecular responses that are seen occur due to the effects of IFNa on JAK2V617F mutant stem cells is debated. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6885

16 Samples

Download data: TXT

(Submitter supplied) JAK2-V617F is the most frequent somatic mutation causing myeloproliferative neoplasm (MPN). JAK2-V617F can be found in healthy individuals with clonal hematopoiesis of indeterminate potential (CHIP) with a frequency much higher than the prevalence of MPN. The factors controlling the conversion of JAK2-V617F CHIP to MPN are largely unknown. We hypothesized that IL-1β mediated inflammation can favor this progression. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

25 Samples

Download data: TSV

(Submitter supplied) Myeloproliferative neoplasms (MPN) are clonal hematopoietic diseases that include essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) as well as BCR-ABL+ chronic myelogenous leukemia (CML). In the past several years, studies with cDNA microarrays have defined patterns of gene expression corresponding to specific molecular abnormalities, oncologic phenotypes, and clinical outcomes in hematologic malignancies. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL18390 GPL18389

45 Samples

Download data: GPR

(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