title: Thrombocytosis and STAT5 activation in chronic myelogenous leukaemia are not associated with JAK2 V617F or calreticulin mutations.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Turakhia
authors.affiliation: Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Gurunathan
authors.initials: G
authors.lastname: Murugesan
authors.affiliation: Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Claudiu V
authors.initials: CV
authors.lastname: Cotta
authors.affiliation: Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Theil
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D037282:Calreticulin / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D005091:Exons; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D013920:Thrombocythemia, Essential / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D013922:Thrombocytosis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism
chemical_list: D037282:Calreticulin; D050799:STAT5 Transcription Factor; D016044:Fusion Proteins, bcr-abl; D053614:Janus Kinase 2
keywords: CHRONIC MYELOID LEUKAEMIA; CYTOGENETICS; HAEMATOPATHOLOGY; MYELOPROLIFERATIVE DISEASE; THROMBOCYTHAEMIA