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Leukemia. 2016 Jan;30(1):131-5. doi: 10.1038/leu.2015.192. Epub 2015 Jul 23.

A new monoclonal antibody (CAL2) detects CALRETICULIN mutations in formalin-fixed and paraffin-embedded bone marrow biopsies.

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Reference and Consultation Center for Lymphoma and Haematopathology, Pathodiagnostik Berlin, Berlin, Germany.
Synaptic Systems GmbH, Göttingen, Germany.
Praxis für Onkologie, Lüdenscheid, Germany.
Senckenbergisches Institut für Pathologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Medizinisches Versorgungszentrum am Helios Klinikum Emil von Behring, Labor für molekulare Diagnostik und Mikrobiologie, Berlin, Germany.


Recent advances in the diagnostic of myeloproliferative neoplasms (MPNs) discovered CALRETICULIN (CALR) mutations as a major driver in these disorders. In contrast to JAK2 mutations being mainly associated with polycythaemia vera, CALR mutations are only associated with primary myelofibrosis (PMF) and essential thrombocythaemia (ET). CALR mutations are present in the majority of PMF and ET patients lacking JAK2 and MPL mutations. As these CALR mutations are absent from reactive bone marrow (BM) lesions their presence indicates ET or PMF. So far these mutations are detectable only by molecular assays. Their molecular detection is cumbersome because of the great CALR mutation heterogeneity. Therefore, the availability of a simple assay would be of great help. All CALR mutations reported lead to a frameshift generating a new 36 amino-acid C-terminus. We generated a monoclonal antibody (CAL2) to this C-neoterminus by immunizing mice with a representative peptide and compared its performance with Sanger sequencing data in 173 MPNs and other BM diseases. There was a 100% correlation between the molecular and the CAL2 immunohistochemical (IHC) assays. Thus, the detection of CALR mutations by the CAL2 IHC is a specific, sensitive, rapid, simple and low-cost method.

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