Thrombocytosis and STAT5 activation in chronic myelogenous leukaemia are not associated with JAK2 V617F or calreticulin mutations

J Clin Pathol. 2016 Aug;69(8):713-9. doi: 10.1136/jclinpath-2015-203498. Epub 2016 Jan 11.

Abstract

Aims: Marked thrombocytosis is uncommon in chronic myelogenous leukaemia (CML) but may be associated with mutation of JAK2 V617F, calreticulin (CALR) and/or phospho-STAT5 (p-STAT5) activation in other myeloproliferative neoplasms (MPNs), particularly essential thrombocythaemia (ET). We investigated the JAK2 V617F, CALR and STAT5 activation status in patients with CML and thrombocytosis (CML-T) that mimicked ET, trying to identify a common mechanism for thrombocytosis in MPN.

Methods: Blood and bone marrow morphological findings were reviewed from seven CML-T, four otherwise typical CML and one CML in blast phase. All cases were analysed for BCR-ABL1, JAK2 V617F and CALR exon 9 mutation and p-STAT5 expression.

Results: Four of seven cases of CML-T had marked thrombocytosis (>1000×10(9)/L). Eleven of 12 cases had megakaryocyte morphology typical for CML. All cases were BCR-ABL1 positive. Eleven of 12 cases were negative for JAK2 V617F, while STAT5 was activated in six of seven CML-T and in four of five CML cases. No case had a detectable CALR exon 9 mutation. One case of CML developed ET-like morphology and had JAK2 V617F detected while in molecular remission for CML.

Conclusions: Detection of BCR-ABL1 is critical in the distinction of ET from CML. Thrombocytosis and STAT5 activation in CML-T are not consistently associated with CALR exon 9 or JAK2 V617F mutation.

Keywords: CHRONIC MYELOID LEUKAEMIA; CYTOGENETICS; HAEMATOPATHOLOGY; MYELOPROLIFERATIVE DISEASE; THROMBOCYTHAEMIA.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Calreticulin / genetics*
  • Calreticulin / metabolism
  • Diagnosis, Differential
  • Exons
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Janus Kinase 2 / genetics*
  • Janus Kinase 2 / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Male
  • Middle Aged
  • Mutation*
  • Phosphorylation
  • STAT5 Transcription Factor / metabolism*
  • Thrombocythemia, Essential / diagnosis*
  • Thrombocythemia, Essential / genetics
  • Thrombocythemia, Essential / metabolism
  • Thrombocytosis / complications
  • Thrombocytosis / diagnosis*
  • Thrombocytosis / genetics
  • Thrombocytosis / metabolism

Substances

  • Calreticulin
  • STAT5 Transcription Factor
  • Fusion Proteins, bcr-abl
  • Janus Kinase 2