Annals of Hematology

, Volume 96, Issue 5, pp 725–732 | Cite as

Clinicopathological differences exist between CALR- and JAK2-mutated myeloproliferative neoplasms despite a similar molecular landscape: data from targeted next-generation sequencing in the diagnostic laboratory

  • Rishu Agarwal
  • Piers Blombery
  • Michelle McBean
  • Kate Jones
  • Andrew Fellowes
  • Ken Doig
  • Cecily Forsyth
  • David A. Westerman
Original Article


Mutations in CALR have recently been detected in JAK2-negative myeloproliferative neoplasms (MPNs) and are key pathological drivers in these diseases. CALR-mutated MPNs are shown to have numerous clinicopathological differences to JAK2-mutated MPNs. The basis of these differences is poorly understood. It is unknown whether these differences result directly from any differences in intracellular signalling abnormalities induced by JAK2/CALR mutations or whether they relate to other phenomena such as a differing spectrum of genetic lesions between the two groups. We aimed to review the clinicopathological and molecular features of CALR- and JAK2-mutated MPNs from samples referred for diagnostic testing using a custom-designed targeted next-generation sequencing (NGS) panel. Eighty-nine CALR-mutated cases were compared with 70 JAK2-mutated cases. CALR-mutated MPNs showed higher platelet counts and a female predominance as compared to JAK2-mutated MPNs in our cohort. We have also observed differences between CALR mutation subtypes in terms of disease phenotype, mutational frequency and allelic burden. Type 1 CALR mutations were found to be more common in myelofibrosis, associated with a higher frequency and number of additional mutations and a higher mutant allelic burden as compared to type 2 CALR mutations. Despite these biological differences, our molecular characterisation suggests that CALR- and JAK2-mutated MPNs are broadly similar in terms of the quantity, frequency and spectrum of co-occurring mutations and therefore observed biological differences are likely to not be heavily influenced by the nature and quantity of co-mutated genes.


Myeloproliferative neoplasms Primary myelofibrosis Essential thrombocythaemia Calreticulin Targeted amplicon sequencing 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Division of Cancer Medicine, Department of PathologyPeter MacCallum Cancer CentreMelbourneAustralia
  2. 2.Bioinformatics CorePeter MacCallum Cancer CentreMelbourneAustralia
  3. 3.University of MelbourneMelbourneAustralia
  4. 4.Jarrett Street Specialist CentreGosfordAustralia

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