Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia

Chih Cheng Chen, Jyh Pyng Gau, Hui Ju Chou, Jie Yu You, Cih En Huang, Yi Yang Chen, Jrhau Lung, Yi Sheng Chou, Yu Wei Leu, Chang Hsien Lu, Kuan Der Lee, Ying Huang Tsai

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Abstract

Calreticulin (CALR) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients, CALR mutations were detected in 33 (22.5 %), JAK2V617F in 94 (63.9 %), and MPL mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (CALR, JAK2V617F, and MPL; triple negative). Interestingly, one patient with the type 2 CALR mutation also harbored a low allele burden (0.025 %) of JAK2V617F mutation. Furthermore, we found a novel CALR mutation, with the resultant protein sharing an identical amino acid sequence to the type 6 CALR mutant. Compared to those with JAK2 mutation, CALR-mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis. CARL mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in JAK2-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of CALR mutations, and a lower platelet count (<1,000 × 109/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that CALR mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.

Original languageEnglish
Pages (from-to)2029-2036
Number of pages8
JournalAnnals of Hematology
Volume93
Issue number12
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Calreticulin
Essential Thrombocythemia
Mutation
Thrombosis
Platelet Count
Survival
Primary Myelofibrosis
Leukocyte Count
Amino Acid Sequence

Keywords

  • CALR mutation
  • Essential thrombocythemia
  • JAK2 mutation
  • MPL mutation
  • Myeloproliferative neoplasm

ASJC Scopus subject areas

  • Hematology

Cite this

Chen, C. C., Gau, J. P., Chou, H. J., You, J. Y., Huang, C. E., Chen, Y. Y., ... Tsai, Y. H. (2014). Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia. Annals of Hematology, 93(12), 2029-2036. https://doi.org/10.1007/s00277-014-2151-8

Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia. / Chen, Chih Cheng; Gau, Jyh Pyng; Chou, Hui Ju; You, Jie Yu; Huang, Cih En; Chen, Yi Yang; Lung, Jrhau; Chou, Yi Sheng; Leu, Yu Wei; Lu, Chang Hsien; Lee, Kuan Der; Tsai, Ying Huang.

In: Annals of Hematology, Vol. 93, No. 12, 2014, p. 2029-2036.

Research output: Contribution to journalArticle

Chen, CC, Gau, JP, Chou, HJ, You, JY, Huang, CE, Chen, YY, Lung, J, Chou, YS, Leu, YW, Lu, CH, Lee, KD & Tsai, YH 2014, 'Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia', Annals of Hematology, vol. 93, no. 12, pp. 2029-2036. https://doi.org/10.1007/s00277-014-2151-8
Chen, Chih Cheng ; Gau, Jyh Pyng ; Chou, Hui Ju ; You, Jie Yu ; Huang, Cih En ; Chen, Yi Yang ; Lung, Jrhau ; Chou, Yi Sheng ; Leu, Yu Wei ; Lu, Chang Hsien ; Lee, Kuan Der ; Tsai, Ying Huang. / Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia. In: Annals of Hematology. 2014 ; Vol. 93, No. 12. pp. 2029-2036.
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abstract = "Calreticulin (CALR) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients, CALR mutations were detected in 33 (22.5 {\%}), JAK2V617F in 94 (63.9 {\%}), and MPL mutations in 4 (2.7 {\%}). Sixteen (10.9 {\%}) patients were negative for all three mutations (CALR, JAK2V617F, and MPL; triple negative). Interestingly, one patient with the type 2 CALR mutation also harbored a low allele burden (0.025 {\%}) of JAK2V617F mutation. Furthermore, we found a novel CALR mutation, with the resultant protein sharing an identical amino acid sequence to the type 6 CALR mutant. Compared to those with JAK2 mutation, CALR-mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis. CARL mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in JAK2-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of CALR mutations, and a lower platelet count (<1,000 × 109/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that CALR mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.",
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AU - Chen, Chih Cheng

AU - Gau, Jyh Pyng

AU - Chou, Hui Ju

AU - You, Jie Yu

AU - Huang, Cih En

AU - Chen, Yi Yang

AU - Lung, Jrhau

AU - Chou, Yi Sheng

AU - Leu, Yu Wei

AU - Lu, Chang Hsien

AU - Lee, Kuan Der

AU - Tsai, Ying Huang

PY - 2014

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N2 - Calreticulin (CALR) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients, CALR mutations were detected in 33 (22.5 %), JAK2V617F in 94 (63.9 %), and MPL mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (CALR, JAK2V617F, and MPL; triple negative). Interestingly, one patient with the type 2 CALR mutation also harbored a low allele burden (0.025 %) of JAK2V617F mutation. Furthermore, we found a novel CALR mutation, with the resultant protein sharing an identical amino acid sequence to the type 6 CALR mutant. Compared to those with JAK2 mutation, CALR-mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis. CARL mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in JAK2-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of CALR mutations, and a lower platelet count (<1,000 × 109/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that CALR mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.

AB - Calreticulin (CALR) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients, CALR mutations were detected in 33 (22.5 %), JAK2V617F in 94 (63.9 %), and MPL mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (CALR, JAK2V617F, and MPL; triple negative). Interestingly, one patient with the type 2 CALR mutation also harbored a low allele burden (0.025 %) of JAK2V617F mutation. Furthermore, we found a novel CALR mutation, with the resultant protein sharing an identical amino acid sequence to the type 6 CALR mutant. Compared to those with JAK2 mutation, CALR-mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis. CARL mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in JAK2-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of CALR mutations, and a lower platelet count (<1,000 × 109/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that CALR mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.

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KW - Essential thrombocythemia

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KW - MPL mutation

KW - Myeloproliferative neoplasm

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