Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin.

Authors: Ding, J  Komatsu, H  Wakita, A  Kato-Uranishi, M  Ito, M  Satoh, A  Tsuboi, K  Nitta, M  Miyazaki, H  Iida, S  Ueda, R 
Citation: Ding J, etal., Blood. 2004 Jun 1;103(11):4198-200. Epub 2004 Feb 5.
Pubmed: (View Article at PubMed) PMID:14764528
DOI: Full-text: DOI:10.1182/blood-2003-10-3471

One Japanese pedigree of familial essential thrombocythemia (FET) inherited in an autosomal-dominant manner is presented. A unique point mutation, serine 505 to asparagine 505 (Ser505Asn), was identified in the transmembrane domain of the c-MPL gene in all of the 8 members with thrombocythemia, but in none of the other 8 unaffected members in this FET family. The Ba/F3 cells expressing the mutant Asn505 acquired interleukin 3 (IL-3)-independent survival capacity, whereas those expressing wild-type Ser505 did not. The autonomous phosphorylation of Mek1/2 and Stat5b was observed in the mutant Ba/F3 cells in the absence of IL-3. The former was also found in platelets derived from the affected individual in the absence of thrombopoietin. These results show that the Asn505 is an activating mutation with respect to the intracellular signaling and survival of the cells. This is the first report of FET deriving from a dominant-positive activating mutation of the c-MPL gene.


Disease Annotations
Phenotype Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 10449014
Created: 2015-12-11
Species: All species
Last Modified: 2015-12-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.