Abstract
Testing for the CALR mutation is included in the updated WHO criteria for essential thrombocythaemia (ET) and primary myelofibrosis (PMF). We report on the application of the CAL2 monoclonal antibody, raised against the mutated CALR gene to myeloid cases. The immunostain was used on 116 acute myeloid leukaemias (AML) and 66 myeloproliferative neoplasms (MPN) or myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN). None of AML cases was stained by the CAL2 antibody, while 20/66 MPNs and MDS/MPNs appeared positive. Fourteen of the latter cases were studied by molecular techniques, and all showed aberrations of the CALR gene. In addition, CAL2 positivity was found in some small‐sized elements besides megakaryocytes. By double staining, these elements corresponded to small megakaryocytes as well as both erythroid and myeloid precursors. This finding suggests possible occurrence of CALR gene abnormalities in a stem cell.
Highlights
The discovery of mutated Calreticulin (CALR) in myeloproliferative neoplasms (MPN) has provided proof of clonality, diagnostic importance and influence on prognosis of this pathology
For some cases included in this study, molecular analysis of CARL gene and a set of other genes including JAK2, MPL, BCR/ ABL1 and KIT were performed using a combination of fragment analysis and sequencing
Unlike JAK2 and MPL point mutations, CALR mutations are highly heterogeneous, with several types of insertions or deletions, all located in exon 9.5 Because of this high heterogeneity, the molecular assays are complicated
Summary
The discovery of mutated Calreticulin (CALR) in myeloproliferative neoplasms (MPN) has provided proof of clonality, diagnostic importance and influence on prognosis of this pathology. The identification of this MPN-associated driver mutation—currently based on molecular assays— is represented as a major diagnostic criterion for essential thrombocythaemia (ET), prefibrotic myelofibrosis and primary myelofibrosis (PMF) in the updated World. Cases of acute myeloid leukaemia (AML) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) have been investigated to assess the specificity of CAL2 antibody. For this purpose, the result of the CAL2 immunostaining was compared with the result of molecular assays. We investigated by double staining whether expression of mutated CALR can be demonstrated on cells of the erythroid and myeloid lineage
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