The authors show that the diverse mutations in CALR that occur in nonmutated JAK2 myeloproliferative diseases all introduce frameshift mutations that alter the C-terminal part of the protein and affect its distribution within cells. The myeloproliferative neoplasms are chronic myeloid cancers that are characterized by the overproduction of mature blood cells, and that may evolve into acute myeloid leukemia. 1 , 2 In addition to chronic myeloid leukemia with the BCR-ABL fusion gene, the three most common myeloproliferative neoplasms are essential thrombocythemia, polycythemia vera, and myelofibrosis. Many patients with a BCR-ABL– negative myeloproliferative neoplasm carry a Janus kinase 2 ( JAK2 ) V617F mutation. 3 – 6 The JAK2 V617F mutation or JAK2 exon 12 mutations are found in most patients with polycythemia vera, 7 , 8 whereas the JAK2 V617F mutation is found in only 50 to 60% of . . .