International Journal of Gerontology 8 (2014) 105
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International Journal of Gerontology
journal homepage: www.ijge-online.com
Letter to the Editor
CALR Mutations in Myeloproliferative Neoplasms*
To the Editor,
The discovery of the JAK2V617F mutation has provided impor-
tant insight into the pathogenesis of BCR-ABL1-negative myelopro-
liferative neoplasms (MPNs) and has revolutionized the diagnosis
and treatment of MPNs. Following JAK2V617F mutation, somatic
mutations such as JAK2 exon 12, MPL, LNK, TET2, DNMT3A, IDH1/2,
ASXL1, EZH2, SRSF2, and SF3B1 have been identified in MPNs. We
have recently reported the frequency of JAK2V617F and DNMT3A
mutations in adult Taiwanese patients with BCR-ABL1-negative
MPNs, and the results are comparable with those in Western coun-
tries1,2. However, JAK2V617F, MPL, and DNMT3A mutations were not
detected in approximately 40% of patients with essential thrombo-
cythemia (ET) in our cohort and others’ cohorts. With the help of
the next-generation sequencing technique, two study groups
have recently demonstrated a high frequency of calreticulin
(CALR) exon 9 mutations in patients with JAK2V617F-negative ET
and primary myelofibrosis3,4. What is important is that both studies
showed that CALR exon 9 mutations are mutually exclusive with
JAK2V617F and MPL mutations, and are not found in patients with
polycythemia vera. In screening tests, CALR mutations are also pre-
sent in a few other myeloid neoplasms such as myelodysplastic
syndrome, but are absent in solid cancers. The discovery of CALR
mutations in patients with JAK2 and MPL unmutated ET and pri-
mary myelofibrosis has largely filled the gap. We therefore propose
that CALR mutations should be screened for during the work up of
MPNs, especially in patients without the JAK2V617F mutation.
Calreticulin is a calcium (Ca2þ)-binding chaperone in the endo-
plasmic reticulum. It has an essential role in ensuring proper protein
and glycoprotein folding. The unexpected discovery of CALR muta-
tions in MPNs has provided an important clue to the novel biological
role of CALR in hematopoiesis. It has also opened a new avenue for
basic, clinical, and translational research in the field of MPNs.
References
1. Lin H-C, Chen CG-S, Chang M-C, et al. JAK2 V617F mutation in adult Taiwanese
patients with essential thrombocythemia: more prevalent in old patients and
correlated with higher hemoglobin level and higher leukocyte count. Int J Geron-
tol. 2013;7:40e44.
2. Lin H-C, Wang S-C, Chen CG-S, et al. Mutation and lineage analysis of DNMT3A in
BCR-ABL1-negative chronic myeloproliferative neoplasms. Int J Gerontol. 2013;7:
186e188.
3. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin
in myeloproliferative neoplasms. N Engl J Med. 2013;369:2379e2390.
4. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloprolifer-
ative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369:2391e2405.
*
Conflicts of interest: All authors have no financial interests to declare related to the material in the manuscript.
http://dx.doi.org/10.1016/j.ijge.2014.03.001
1873-9598/Copyright © 2014, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. All rights reserved.
Ken-Hong Lim*
Division of Hematology and Oncology, Department of Internal Medicine,
Mackay Memorial Hospital, Taiwan
Laboratory of Good Clinical Research Center, Department of Medical Research,
Mackay Memorial Hospital, Tamsui District, Taiwan
Graduate Institute of Oncology, National Taiwan University College of Medicine,
Taipei, Taiwan
Mackay Medical College, New Taipei City, Taiwan
Huan-Chau Lin
Division of Hematology and Oncology, Department of Internal Medicine,
Mackay Memorial Hospital, Taiwan
Laboratory of Good Clinical Research Center, Department of Medical Research,
Mackay Memorial Hospital, Tamsui District, Taiwan
Caleb Gon-Shen Chen
Division of Hematology and Oncology, Department of Internal Medicine,
Mackay Memorial Hospital, Taiwan
Laboratory of Good Clinical Research Center, Department of Medical Research,
Mackay Memorial Hospital, Tamsui District, Taiwan
Institute of Molecular Medicine, National Tsing-Hua University, Hsin-Chu,
Taiwan
Yi-Hao Chiang
Division of Hematology and Oncology, Department of Internal Medicine,
Mackay Memorial Hospital, Taiwan
Laboratory of Good Clinical Research Center, Department of Medical Research,
Mackay Memorial Hospital, Tamsui District, Taiwan
Chung-Der Hsiao
Department of Bioscience Technology, Chung Yuan Christian University,
Chung-Li, Taiwan
Yuan-Yeh Kuo
Graduate Institute of Oncology, National Taiwan University College of Medicine,
Taipei, Taiwan
*
Correspondence to: Dr Ken-Hong Lim, MD, Division of Hematology and
Oncology, Department of Internal Medicine, Mackay Memorial Hospital,
Number 92, Section 2, Chungshan North Road, Taipei 10449, Taiwan.
E-mail address: limkenhong@gmail.com (K.-H. Lim).
5 September 2013
Available online 3 June 2014