title: Phospho-STAT5 expression pattern with the MPL W515L mutation is similar to that seen in chronic myeloproliferative disorders with JAK2 V617F.
abstract: Abnormal nuclear megakaryocytic staining for phospho-STAT5 (pSTAT5) correlates with JAK2 V617F mutational status in non-chronic myelogenous leukemia chronic myeloproliferative disorders. However, a proportion of wild-type JAK2 non-chronic myelogenous leukemia chronic myeloproliferative disorders cases also demonstrate this abnormal pSTAT5 expression pattern. We report a patient with a JAK2 V617F-negative myeloproliferative/myelodysplastic syndrome who had abnormal megakaryocytic pSTAT5 expression and a MPL W515L mutation. The patient was a 71-year-old man with anemia and thrombocythemia on laboratory examination. His peripheral blood smear demonstrated occasional dysplastic neutrophils. Bone marrow biopsy revealed hypercellular marrow with features consistent with myeloproliferative/myelodysplastic syndrome. Immunohistochemistry for pSTAT5 showed abnormal nuclear megakaryocyte positivity. Cytogenetic analysis revealed a normal karyotype, fluorescence in situ hybridization for BCR-ABL was negative, and JAK2 genotyping demonstrated wild-type JAK2. However, MPL genotyping showed a MPL W515L mutation. Abnormal nuclear megakaryocytic staining for pSTAT5 expression, previously associated with the JAK2 V617F mutation, is also associated with MPL W515L, likely reflecting activation of the JAK-STAT signaling pathway.
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gibson
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Schade
authors.forename: Hadrian
authors.initials: H
authors.lastname: Szpurka
authors.forename: Beata
authors.initials: B
authors.lastname: Bak
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology; D054437:Myelodysplastic-Myeloproliferative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D050799:STAT5 Transcription Factor / Q000378:metabolism*
chemical_list: D053628:Receptors, Thrombopoietin; D050799:STAT5 Transcription Factor; C082218:MPL protein, human; D016044:Fusion Proteins, bcr-abl; C507924:JAK2 protein, human; D053614:Janus Kinase 2