GEO DataSets

(Submitter supplied) In this dataset, we compare the gene expression data of induced pluripotent stem (iPS) cell-derived CD61+ megakaryocytes carrying heterozygous or homozygous Calreticulin (CALR) ins5 mutations or the CALR wildtype gene.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

9 Samples

Download data: CSV

(Submitter supplied) Somatic mutations in calreticulin (CALR) are present in approximately 40% of patients with myeloproliferative neoplasms (MPN). However, the mechanism by which mutant CALR is oncogenic is unknown. Here, we demonstrate that a megakaryocytic-specific MPN phenotype is induced when mutant CALR is over-expressed in mice and that the thrombopoietin receptor, MPL is required for mutant CALR driven transformation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

12 Samples

Download data: TSV

(Submitter supplied) Recurrent mutations in calreticulin (CALR) are present in 70-80% of JAK2 unmutated myeloproliferative neoplasms (MPN). Current models of CALR mutant MPNs are mainly based on cancer cell lines with ectopic overexpression or transgenic mouse models with a lack of data for primary human hematopoietic stem and progenitor cells (HSPCs) with endogenous CALR expression. Thus, we developed a CRISPR/Cas9 and AAV6-mediated knock-in approach to introduce the two most common CALR mutations (52 bp deletion, DEL; 5 bp insertion, INS) at the endogenous gene locus in human cord blood-derived HSPCs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21290

9 Samples

Download data: TSV

(Submitter supplied) Cancer is driven by somatic mutations that provide a fitness advantage. While targeted therapies often focus on the mutated gene or its direct downstream effectors, imbalances brought on by cell-state alterations may also confer unique vulnerabilities. In myeloproliferative neoplasms (MPN), somatic mutations in the calreticulin (CALR) gene are disease-initiating through aberrant binding of mutant CALR to the thrombopoietin receptor MPL and ligand-independent activation of JAK-STAT signaling. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

7 Samples

Download data: TXT

(Submitter supplied) Gene expression of hematopoietic stem/progenitor cells from mice with frameshifted Calr was examined.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

3 Samples

Download data: XLSX

(Submitter supplied) Mutations in the endoplasmic reticulum (ER) chaperone calreticulin (CALR) are common in myeloproliferative neoplasm (MPN) patients, activate the thrombopoietin receptor (MPL), and mediate constitutive JAK/STAT signaling. The mechanisms by which CALR mutations cause myeloid transformation are incompletely defined. We employed mass spectrometry proteomics to identify novel CALR-mutant interacting proteins. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

8 Samples

Download data: BW

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

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4685

116 Samples

Download data: CEL

(Submitter supplied) We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4685

12 Samples

Download data: CEL

(Submitter supplied) We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4685

104 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; Other

Platforms:

GPL24247 GPL13112

18 Samples

Download data

(Submitter supplied) RNA-sequencing of megakaryocyte-erythroid progenitors of CALRdel52/+ MxCre mice treated with either vehicle or 2-deoxy-D-glucose for 21 days.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

16 Samples

Download data: TSV

(Submitter supplied) Calreticulin (CALR) mutations are frequent, disease-initiating events in myeloproliferative neoplasms (MPN). Although the biological mechanism by which CALR mutations cause MPN has been elucidated, there currently are no clonally selective therapies for CALR-mutant MPN. To identify unique genetic dependencies in CALR-mutant MPN, we performed a whole-genome CRISPR knockout depletion screen in mutant CALR-transformed hematopoietic cells. more...

Organism:

Mus musculus

Type:

Other

Platform:

GPL13112

1 Sample

Download data: CSV, TXT

(Submitter supplied) Calreticulin (CALR) mutations are frequent, disease-initiating events in myeloproliferative neoplasms (MPN). Although the biological mechanism by which CALR mutations cause MPN has been elucidated, there currently are no clonally selective therapies for CALR-mutant MPN. To identify unique genetic dependencies in CALR-mutant MPN, we performed a whole-genome CRISPR knockout depletion screen in mutant CALR-transformed hematopoietic cells. more...

Organism:

Mus musculus

Type:

Other

Platform:

GPL13112

1 Sample

Download data: CSV, TXT, XLSX

(Submitter supplied) Somatic mutations of calreticulin (CALR) have been described in approximately 30-40% of JAK2 and MPL unmutated Essential Thrombocythemia and Primary Myelofibrosis patients. CALR is an endoplasmic reticulum (ER) chaperone responsible for proper protein folding and calcium retention. Recent data demonstrated that the TPO receptor (MPL) is essential for the development of CALR mutant-driven Myeloproliferative Neoplasms (MPNs). more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

18 Samples

Download data: CEL

(Submitter supplied) In this work, we compared gene expression profile (GEP) of K562 cells transduced with the retroviral vector LCALRins5IDN or LCALRdel52IDN with K562 cells transduced with LwtCALRIDN In order to unravel MPL-independent mechanisms underlying the effect of CALR mutations on MPN pathogenesis, we analysed the transcriptional changes induced by the CALRins5 or CALRdel52 overexpression in K562 cells, which lack MPL expression

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL13667

9 Samples

Download data: CEL

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

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL16791 GPL22245 GPL15520

28 Samples

Download data: MTX, TSV, TXT

(Submitter supplied) Somatic cancer driver mutations may result in distinctly diverging phenotypic outputs. Thus, a common driver lesion may result in cancer subtypes with distinct clinical presentations and outcomes. The diverging phenotypic outputs of mutations result from the superimposition of the mutations with distinct progenitor cell populations that have differing lineage potential. However, our ability to test this hypothesis has been challenged by currently available tools. more...

Organism:

Homo sapiens; Mus musculus

Type:

Other

Platforms:

GPL16791 GPL15520 GPL22245

16 Samples

Download data: TXT

(Submitter supplied) Somatic cancer driver mutations may result in distinctly diverging phenotypic outputs. Thus, a common driver lesion may result in cancer subtypes with distinct clinical presentations and outcomes. The diverging phenotypic outputs of mutations result from the superimposition of the mutations with distinct progenitor cell populations that have differing lineage potential. However, our ability to test this hypothesis has been challenged by currently available tools. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL22245 GPL16791

12 Samples

Download data: MTX, TSV

(Submitter supplied) Frameshift mutations in CALR (calreticulin) are associated with essential thrombocythaemia (ET), but the stages at and mechanisms by which mutant CALR drives transformation remain incompletely defined. Here, we use single-cell approaches to examine the haematopoietic stem/progenitor cell (HSPC) landscape in a mouse model of mutant CALR-driven ET. We identify a trajectory linking HSCs with megakaryocytes, and prospectively identify a novel intermediate population that is overrepresented in the disease state. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

8 Samples

Download data: H5