TY - JOUR
T1 - Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia
T2 - A collaborative study of 1027 patients
AU - Tefferi, Ayalew
AU - Wassie, Emnet A.
AU - Guglielmelli, Paola
AU - Gangat, Naseema
AU - Belachew, Alem A.
AU - Lasho, Terra L.
AU - Finke, Christy
AU - Ketterling, Rhett P.
AU - Hanson, Curtis A.
AU - Pardanani, Animesh
AU - Wolanskyj, Alexandra P.
AU - Maffioli, Margherita
AU - Casalone, Rosario
AU - Pacilli, Annalisa
AU - Vannucchi, Alessandro M.
AU - Passamonti, Francesco
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.23743
DO - 10.1002/ajh.23743
M3 - Article
C2 - 24753125
AN - SCOPUS:84904401956
SN - 0361-8609
VL - 89
SP - E121-E124
JO - American journal of hematology
JF - American journal of hematology
IS - 8
ER -