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Calreticulin gene exon 9 frameshift mutations in patients with thrombocytosis Leukemia (2014) 28, 1152–1154; doi:10.1038/leu.2013.382 Somatic frameshift mutations in exon 9 of the calreticulin (CALR) gene were recently identified in patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs), particularly essential thrombocythemia and myelofibrosis.1,2 Calreticulin is a highly conserved endoplasmic reticulum (ER) luminal Ca2þ-binding chaperone protein with a critical role in the process of glycoprotein folding and a number of other cellular functions both inside and outside the ER,3,4 and has three domains with different structural and functional properties; a globular N domain, a proline-rich P domain and an acidic C domain.3,4 The disrupted C-terminal region contains a KDEL ER-retention sequence multiple sites with high capacity for Ca2þ bindin