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CALR mutations are infrequent in WHO-defined refractory anemia with ring sideroblasts

Leukemia volume 28, pages 1370–1371 (2014)Cite this article

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Somatic mutations involving the calreticulin (CALR) gene have recently been reported in JAK2- and MPL-unmutated patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET).1, 2 Most of these mutations are located in exon 9 (somatic insertions or deletions), generating a +1-bp frameshift, resulting in a mutant protein with a novel C-terminal. With the exception of rare instances of mutant CALR and JAK2 coexpression,3 CALR mutations are mutually exclusive of JAK2 and MPL mutations and are seen in 49–74% of patients with JAK2/MPL-negative ET or PMF.3, 4 The clinical course of CALR-mutated patients was reported to be more indolent, with a lower risk of thrombosis in ET and a better overall survival in PMF.3, 4

Klampf et al.1 did not find CALR mutations in other myeloid neoplasms, with the exception of refractory anemia with ring sideroblasts and marked thrombocytosis (RARS-T); 3 (12.5%) of their 24 patients with RARS-T-expressed CALR mutations and all three were JAK2/MPL negative and SF3B1 mutated. SF3B1 is a spliceosome component gene whose mutation is strongly associated with the presence of bone marrow (BM) ring sideroblasts.5, 6 In the study by Nangalia et al.,2 CALR mutations were not seen in 6 patients with RARS-T but were reported in 3 (11%) of 27 patients with RARS. We undertook the current study to further clarify the incidence of CALR mutations in strictly World Health Organization (WHO)-defined RARS.7

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References

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    M M Patnaik, A Belachew, C Finke, T L Lasho, C A Hanson & A Tefferi

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  1. M M Patnaik
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  2. A Belachew
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  3. C Finke
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  4. T L Lasho
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  5. C A Hanson
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  6. A Tefferi
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Correspondence to A Tefferi.

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Patnaik, M., Belachew, A., Finke, C. et al. CALR mutations are infrequent in WHO-defined refractory anemia with ring sideroblasts. Leukemia 28, 1370–1371 (2014). https://doi.org/10.1038/leu.2014.47

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