Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia: A collaborative study of 1027 patients. Issue 8 (16th May 2014)

• Record Type: Journal Article
• Authors: Tefferi, Ayalew; Wassie, Emnet A.; Guglielmelli, Paola; Gangat, Naseema; Belachew, Alem A.; Lasho, Terra L.; Finke, Christy; Ketterling, Rhett P.; Hanson, Curtis A.; Pardanani, Animesh; Wolanskyj, Alexandra P.; Maffioli, Margherita; Casalone, Rosario; Pacilli, Annalisa; Vannucchi, Alessandro M.; Passamonti, Francesco
• Is Part Of: American journal of hematology. Volume 89:Issue 8(2014:Aug.)
• Page Start: E121
• Page End: E124
• Publication Date: 2014-05-16
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.23743
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>CALR</italic> (calreticulin) trails <italic>JAK</italic>2 as the second most mutated gene in essential thrombocythemia (ET). Mutant <italic>CALR</italic> 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 (<italic>n</italic> = 402) and validation (<italic>n</italic> = 625) cohorts. Among the 402 ET patients in the test cohort, 227 (57%) harbored <italic>JAK</italic>2, 11 (3%) Myeloproliferative leukemia virus oncogene (<italic>MPL</italic>), and 114 (28%) <italic>CALR</italic> mutations; 12% were wild‐type for all three mutations (i.e., triple‐negative). Among the 114 patients with <italic>CALR</italic> mutations, 51 (45%) displayed type‐1 and 44 (39%) type‐2 variants; compared to mutant <italic>JAK</italic>2, both variants were associated with higher platelet and lower hemoglobin and leukocyte counts. However, male sex was associated with only type‐1 (<italic>P</italic> = 0.005) and younger age with type‐2 (<italic>P</italic> = 0.001) variants. Notably, platelet count was significantly higher in type‐2 vs. type‐1 <italic>CALR</italic>‐mutated patients (<italic>P</italic> = 0.03) and the particular observation was validated in the validation cohort that included 111 <italic>CALR</italic>‐mutated ET patients (<italic>P</italic> = 0.002). These findings, coupled with the recent demonstration of preferential expression of mutant and wild‐type <italic>CALR</italic> in megakaryocytes, suggest differential effects of <italic>CALR</italic> variants on thrombopoiesis. Am. J. Hematol. 89:E121–E124, 2014. © 2014 Wiley Periodicals, Inc.</p> </abstract>