TY - JOUR
T1 - Calreticulin variant stratified driver mutational status and prognosis in essential thrombocythemia
AU - Elala, Yoseph C.
AU - Lasho, Terra L.
AU - Gangat, Naseema
AU - Finke, Christy
AU - Barraco, Daniela
AU - Haider, Mahnur
AU - Abou Hussein, Ahmed K.
AU - Hanson, Curtis A.
AU - Ketterling, Rhett P.
AU - Pardanani, Animesh
AU - Tefferi, Ayalew
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - About 85% of patients with essential thrombocythemia (ET) harbor one of three driver mutations: JAK2, calreticulin (CALR), and MPL; the remaining ( ∼15%) are wild type for all three mutations and are referred to as being "triple negative." Furthermore, CALR mutations in ET are structurally classified as type 1/type 1-like or type 2/type 2-like variants. The objective of the current study was to examine the impact of CALR mutation variant stratified driver mutational status on overall (OS), myelofibrosis-free (MFFS), thrombosis-free, and leukemia-free survival (LFS) in ET; 495 patients (median age 58 years; 61% females) with ET were fully annotated for the their driver mutational status: 321 (65%) harbored JAK2, 109 (22%) CALR, and 12 (2%) MPL mutations and 11% were triple-negative. Among the 109 CALR-mutated cases, 52% were classified as type 1/type 1-like and 48% as type 2/type 2-like. In univariate analysis, triple-negative patients displayed the best and MPL mutated the worst OS (P=0.007); however, the difference in OS was no longer apparent on multivariable analysis that included age and sex as covariates (P=0.5). LFS was also similar among the different mutational groups (P=0.6) whereas MFFS was significantly shorter in MPL-mutated patients on both univariate and multivariable analyses (age-adjusted P=0.02; HR 7.9, 95% CI 2.0-31.5). Also in multivariable analysis that included thrombosis history, age, and cardiovascular risk factors, the presence of JAK2 or MPL mutations was independently associated with higher risk of thrombosis (P=0.02; HR 1.9, 95% CI 1.1-3.4). In conclusion, driver mutational status in ET does not appear to influence overall or LFS, even after CALR variant stratification. However, the presence of MPL mutations might be associated with a higher risk of fibrotic transformation and the presence of JAK2/MPL mutations with higher risk of thrombosis.
AB - About 85% of patients with essential thrombocythemia (ET) harbor one of three driver mutations: JAK2, calreticulin (CALR), and MPL; the remaining ( ∼15%) are wild type for all three mutations and are referred to as being "triple negative." Furthermore, CALR mutations in ET are structurally classified as type 1/type 1-like or type 2/type 2-like variants. The objective of the current study was to examine the impact of CALR mutation variant stratified driver mutational status on overall (OS), myelofibrosis-free (MFFS), thrombosis-free, and leukemia-free survival (LFS) in ET; 495 patients (median age 58 years; 61% females) with ET were fully annotated for the their driver mutational status: 321 (65%) harbored JAK2, 109 (22%) CALR, and 12 (2%) MPL mutations and 11% were triple-negative. Among the 109 CALR-mutated cases, 52% were classified as type 1/type 1-like and 48% as type 2/type 2-like. In univariate analysis, triple-negative patients displayed the best and MPL mutated the worst OS (P=0.007); however, the difference in OS was no longer apparent on multivariable analysis that included age and sex as covariates (P=0.5). LFS was also similar among the different mutational groups (P=0.6) whereas MFFS was significantly shorter in MPL-mutated patients on both univariate and multivariable analyses (age-adjusted P=0.02; HR 7.9, 95% CI 2.0-31.5). Also in multivariable analysis that included thrombosis history, age, and cardiovascular risk factors, the presence of JAK2 or MPL mutations was independently associated with higher risk of thrombosis (P=0.02; HR 1.9, 95% CI 1.1-3.4). In conclusion, driver mutational status in ET does not appear to influence overall or LFS, even after CALR variant stratification. However, the presence of MPL mutations might be associated with a higher risk of fibrotic transformation and the presence of JAK2/MPL mutations with higher risk of thrombosis.
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U2 - 10.1002/ajh.24338
DO - 10.1002/ajh.24338
M3 - Article
C2 - 26890983
AN - SCOPUS:84962858012
SN - 0361-8609
VL - 91
SP - 503
EP - 506
JO - American journal of hematology
JF - American journal of hematology
IS - 5
ER -