Distinct clinical characteristics of myeloproliferative neoplasms with calreticulin mutations
Hajnalka Andrikovics,
Tunde Krahling,
Katalin Balassa,
Gabriella Halm,
Andras Bors,
Magdalena Koszarska,
Arpad Batai,
Janos Dolgos,
Judit Csomor,
Miklos Egyed,
Andrea Sipos,
Peter Remenyi,
Attila Tordai,
Tamas Masszi
Affiliations
Hajnalka Andrikovics
Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest
Tunde Krahling
Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest
Katalin Balassa
Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest
Gabriella Halm
Department of Hematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest
Andras Bors
Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest
Magdalena Koszarska
Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest
Arpad Batai
Department of Hematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest
Janos Dolgos
Department of Hematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest
Judit Csomor
Department of Pathology, St. István and St. Lászlo Hospital, Budapest
Miklos Egyed
Department of Haematology, Kaposi Mor Hospital, Kaposvar
Andrea Sipos
Department of Hematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest
Peter Remenyi
Department of Hematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest
Attila Tordai
Laboratory of Molecular Diagnostics, Hungarian National Blood Transfusion Service, Budapest
Tamas Masszi
Department of Hematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital, Budapest;3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
Somatic insertions/deletions in the calreticulin gene have recently been discovered to be causative alterations in myeloproliferative neoplasms. A combination of qualitative and quantitative allele-specific polymerase chain reaction, fragment-sizing, high resolution melting and Sanger-sequencing was applied for the detection of three driver mutations (in Janus kinase 2, calreticulin and myeloproliferative leukemia virus oncogene genes) in 289 cases of essential thrombocythemia and 99 cases of primary myelofibrosis. In essential thrombocythemia, 154 (53%) Janus kinase 2 V617F, 96 (33%) calreticulin, 9 (3%) myeloproliferative leukemia virus oncogene gene mutation-positive and 30 triple-negative (11%) cases were identified, while in primary myelofibrosis 56 (57%) Janus kinase 2 V617F, 25 (25%) calreticulin, 7 (7%) myeloproliferative leukemia virus oncogene gene mutation-positive and 11 (11%) triple-negative cases were identified. Patients positive for the calreticulin mutation were younger and had higher platelet counts compared to Janus kinase 2 mutation-positive counterparts. Calreticulin mutation-positive patients with essential thrombocythemia showed a lower risk of developing venous thrombosis, but no difference in overall survival. Calreticulin mutation-positive patients with primary myelofibrosis had a better overall survival compared to that of the Janus kinase 2 mutation-positive (P=0.04) or triple-negative cases (P=0.01). Type 2 calreticulin mutation occurred more frequently in essential thrombocythemia than in primary myelofibrosis (P=0.049). In essential thrombocythemia, the calreticulin mutational load was higher than the Janus kinase 2 mutational load (P
