Journal Article

Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2

Avezov, E, McLaren, S, Dimitropoulou, D, Silber, Y, Maclean, C, Jones, A.V, Harding, H.P, Bianchi, M, Cross, N.C.P, Bloxham, D, Papaemmanuil, E, Hinton, J, Campbell, P.J, Robinson, B, Goudie, C.T, Mudie, L, Bowen, D, Loughran, S.J, Maddison, M, Butler, A.P, Martincorena, I, Nice, F.L, Raine, K, Guglielmelli, P, Teague, J.W, Ron, D, Huntly, B.J.P, Tauro, S, Li, J, Hill, K, Jones, D.R, Van Loo, P, Tarpey, P, Gundem, G, Kent, D.G, Greaves, M, Nangalia, J, Ortmann, C.A, Baxter, E.J, Green, A.R, O'Meara, S, Aziz, A, Vannucchi, A.M, Du, M.-Q, Massie, C.E, Wedge, D.C, Orchard, K, Fitzpatrick, J.D, Kollmann, K, Godfrey, A.L, Keohane, C, Harrison, C.N

2013

Overview

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 . . .

• Publisher: Massachusetts Medical Society
• Subject: Amino Acid Sequence / Biological and medical sciences / Bone Marrow Diseases - genetics / Calreticulin / Calreticulin - analysis / Calreticulin - genetics / Cell surface / DNA methylation / Endoplasmic reticulum / Exons / Flow cytometry / General aspects / Golgi cells / Hematopoietic stem cells / Hemoglobin / Humans / Immunofluorescence / Janus kinase / Janus kinase 2 / Janus Kinase 2 - genetics / Kinases / Leukemia / Leukemia, Myeloid - genetics / Localization / Medical research / Medical sciences / Molecular Sequence Data / Mutation / Myelodysplastic syndrome / Myelodysplastic Syndromes - genetics / Myelofibrosis / Neoplasms - genetics / Phylogeny / Polycythemia / Polycythemia vera / Polymerase Chain Reaction / Primary Myelofibrosis - genetics / Progenitor cells / Scholarships & fellowships / Sequence Analysis, DNA / Thrombocythemia, Essential - genetics