CAL2 monoclonal antibody is a rapid and sensitive assay for the detection of calreticulin mutations in essential thrombocythemia patients

Massimiliano Bonifacio, Rachele Montemezzi, Alice Parisi, Giovanna De Matteis, Roberta Bertorelle, Luigi Scaffidi, Cinzia Candiotto, Giuseppe Lippi, Alberto Zamò, Marco Chilosi, Giovanni Pizzolo, Aldo Scarpa, Mauro Krampera

Research output: Contribution to journalArticle

Abstract

Calreticulin (CALR) mutations are detected in the majority of JAK2 wild type patients with essential thrombocythemia (ET). Unlike JAK2V617F and MPL point mutations, CALR mutations are highly heterogeneous, with several types of indels being reported so far. CAL2 is a monoclonal antibody specifically recognizing the C-neoterminal peptide derived from all the frameshift mutations of CALR. We retrospectively analysed 172 ET patients diagnosed at our Institution from 1980 to 2015. In JAK2V617F- and MPLW515K/L-wild type patients CALR mutations were searched on peripheral blood and CAL2 immunostaining was performed on bone marrow. In addition, bone marrow biopsies were histologically reviewed for megakaryocytic features. Thirty-one patients (18%) were CALR-mutated. Concordance between molecular and immunohistological detection of CALR mutations was near complete, albeit a single patient was found to be positive by molecular tests only. Two patterns were defined in CAL2-positive bone marrow samples, characterized by staining of almost only megakaryocytes (pattern A: 41%) or staining of megakaryocytes and ≥ 2% small non megakaryocytic elements (pattern B: 59%), at least partially being myeloid precursors. Pattern B biopsies had higher cellularity and number of megakaryocytes compared to pattern A samples. In this series, CAL2 allowed rapid and cost-efficient identification of CALR-mutated ET patients. The biological significance of different staining pattern should be confirmed in wider and independent series.

Original languageEnglish
Pages (from-to)2339-2346
Number of pages8
JournalAnnals of Hematology
Volume98
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

Keywords

  • CAL2
  • Calreticulin
  • Diagnostic tools
  • Driver mutations
  • Essential thrombocythemia

ASJC Scopus subject areas

  • Hematology

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    Bonifacio, M., Montemezzi, R., Parisi, A., De Matteis, G., Bertorelle, R., Scaffidi, L., Candiotto, C., Lippi, G., Zamò, A., Chilosi, M., Pizzolo, G., Scarpa, A., & Krampera, M. (2019). CAL2 monoclonal antibody is a rapid and sensitive assay for the detection of calreticulin mutations in essential thrombocythemia patients. Annals of Hematology, 98(10), 2339-2346. https://doi.org/10.1007/s00277-019-03741-8