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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 14, 2016 |
| Title |
Physical interaction between mutant calreticulin and the thrombopoietin receptor is required for transformation of hematopoietic cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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. Whole transcriptome analysis reveals enrichment of STAT signatures in mutant CALR transformed cells and JAK2 inhibitor treatment abrogates STAT activation. Employing extensive mutagenesis-based structure-function analysis we demonstrate that the positively charged amino acids within the mutant CALR C-terminus are required for cellular transformation through facilitating physical interaction between mutant CALR and MPL. Together, our findings elucidate a novel mechanism of cancer pathogenesis.
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| Overall design |
Transcriptomes derived from BA/F3-MPL cells transformed with human wild-type CALR, human mutant CALR 52bp del, or Empty vector, at time zero (t0) and 24 hours (t24) after IL3-withdrawal culture were generated by deep sequencing, two replicas, by HiSeq2000.
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| Contributor(s) |
Elf S, Abdelfattah N, Chen E, Perales-Patón J, Rosen E, Ko A, Peisker F, Florescu N, Giannini S, Wolach O, Morgan E, Losman J, Schneider RK, Al-Shahrour F, Mullally A |
| Citation(s) |
26951227 |
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| Submission date |
Nov 10, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Javier Perales-Paton |
| E-mail(s) |
javier.perales@bioquant.uni-heidelberg.de
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| Organization name |
Heidelberg University
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| Department |
Faculty of Medicine
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| Lab |
Institute for Computational Biomedicine
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| Street address |
Im Neuenheimer Feld 267
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| City |
Heidelberg |
| State/province |
Baden-Württemberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA301731 |
| SRA |
SRP066021 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE74890_RAW.tar |
1.2 Mb |
(http)(custom) |
TAR (of TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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