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Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia: A collaborative study of 1027 patients
Author(s) -
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
Publication year - 2014
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23743
Subject(s) - essential thrombocythemia , calreticulin , frameshift mutation , thrombopoietin receptor , wild type , thrombopoiesis , myelofibrosis , exon , medicine , biology , cancer research , polycythemia vera , gastroenterology , genetics , mutant , gene , thrombopoietin , megakaryocyte , bone marrow , stem cell , endoplasmic reticulum , haematopoiesis
CALR (calreticulin) trails JAK 2 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 JAK 2, 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 JAK 2, 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.