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Frameshifting (− 1/+ 2) mutations in the exon 9 of the calreticulin gene (CALR) lead to the development of BCR-ABL-negative myeloproliferative neoplasms (MPNs) in humans under the forms of essential thrombocythemia (ET) and myelofibrosis. 1, 2 We have shown that mutant human CALR proteins require interaction with the thrombopoietin receptor (TpoR) to exert an oncogenic activation of the JAK/STAT pathway. 3, 4 Here, we report that homologous mutations in the murine Calr gene result in a highly similar, but not identical mutant CALR protein as found in human patients that also requires TpoR interaction to be able to activate the JAK/STAT pathway.

CALR is a highly conserved protein throughout the species: 5 both human and mouse CALR transcript sequences share 88% of base-pair identity (1098/1254 bp, human sequence as reference). Similarly, mouse and human wild-type CALR protein amino acid …