Phospho-STAT5 expression pattern with the MPL W515L mutation is similar to that seen in chronic myeloproliferative disorders with JAK2 V617F

Hum Pathol. 2008 Jul;39(7):1111-4. doi: 10.1016/j.humpath.2007.10.034. Epub 2008 May 13.


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.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Fusion Proteins, bcr-abl / metabolism
  • Genotype
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Janus Kinase 2 / genetics*
  • Male
  • Megakaryocytes / metabolism
  • Megakaryocytes / pathology
  • Myelodysplastic-Myeloproliferative Diseases / genetics
  • Myelodysplastic-Myeloproliferative Diseases / metabolism*
  • Myelodysplastic-Myeloproliferative Diseases / pathology
  • Point Mutation*
  • Polymerase Chain Reaction
  • Receptors, Thrombopoietin / genetics*
  • STAT5 Transcription Factor / metabolism*


  • Receptors, Thrombopoietin
  • STAT5 Transcription Factor
  • MPL protein, human
  • Fusion Proteins, bcr-abl
  • JAK2 protein, human
  • Janus Kinase 2