Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia: A collaborative study of 1027 patients |
| |
| Authors: | Ayalew Tefferi Emnet A. Wassie Paola Guglielmelli Naseema Gangat Alem A. Belachew Terra L. Lasho Christy Finke Rhett P. Ketterling Curtis A. Hanson Animesh Pardanani Alexandra P. Wolanskyj Margherita Maffioli Rosario Casalone Annalisa Pacilli Alessandro M. Vannucchi Francesco Passamonti |
| |
| Affiliation: | 1. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota;2. Laboratorio Congiunto MMPC, Department of experimental and clinical medicine, University of Florence, Florence, Italy;3. Division of Cytogenetics, Mayo Clinic, Rochester, Minnesota;4. Division of Hematopathology, Mayo Clinic, Rochester, Minnesota;5. Division of Hematology, Genetic Unit, Medical Genetic and Cytogenetics Laboratory, SSD, SMEL, University Hospital Ospedale di Circolo e Fondazione Macchi, Varese, Italy |
| |
| Abstract: | CALR (calreticulin) trails JAK2 as the second most mutated gene in essential thrombocythemia (ET). Mutant CALR in ET is a result of frameshift mutations, caused by exon 9 deletions or insertions; type‐1, 52‐bp deletion (p.L367fs*46), and type‐2, 5‐bp TTGTC insertion (p.K385fs*47) variants constitute more than 80% of these mutations. The current study includes a total of 1027 patients divided into test (n = 402) and validation (n = 625) cohorts. Among the 402 ET patients in the test cohort, 227 (57%) harbored JAK2, 11 (3%) Myeloproliferative leukemia virus oncogene (MPL), and 114 (28%) CALR mutations; 12% were wild‐type for all three mutations (i.e., triple‐negative). Among the 114 patients with CALR mutations, 51 (45%) displayed type‐1 and 44 (39%) type‐2 variants; compared to mutant JAK2, both variants were associated with higher platelet and lower hemoglobin and leukocyte counts. However, male sex was associated with only type‐1 (P = 0.005) and younger age with type‐2 (P = 0.001) variants. Notably, platelet count was significantly higher in type‐2 vs. type‐1 CALR‐mutated patients (P = 0.03) and the particular observation was validated in the validation cohort that included 111 CALR‐mutated ET patients (P = 0.002). These findings, coupled with the recent demonstration of preferential expression of mutant and wild‐type CALR in megakaryocytes, suggest differential effects of CALR variants on thrombopoiesis. Am. J. Hematol. 89:E121–E124, 2014. © 2014 Wiley Periodicals, Inc. |
| |
| Keywords: | |
|
|
