Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2

Mol Cell. 2000 Sep;6(3):693-704. doi: 10.1016/s1097-2765(00)00067-8.


STAT5 is activated in a broad spectrum of human hematologic malignancies. We addressed whether STAT5 activation is necessary for the myelo- and lymphoproliferative disease induced by TEL/JAK2 using a genetic approach. Whereas mice transplanted with bone marrow transduced with retrovirus expressing TEL/JAK2 develop a rapidly fatal myelo- and lymphoproliferative syndrome, reconstitution with bone marrow derived from Stat5ab-deficient mice expressing TEL/JAK2 did not induce disease. Disease induction in the Stat5a/b-deficient background was rescued with a bicistronic retrovirus encoding TEL/JAK2 and Stat5a. Furthermore, myeloproliferative disease was induced by reconstitution with bone marrow cells expressing a constitutively active mutant, Stat5a, or a single Stat5a target, murine oncostatin M (mOSM). These data define a critical role for Stat5a/b and mOSM in the pathogenesis of TEL/JAK2 disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Southern
  • Bone Marrow Cells / pathology
  • Bone Marrow Transplantation
  • Colony-Forming Units Assay
  • DNA, Neoplasm / analysis
  • DNA-Binding Proteins / genetics*
  • Fibrosis
  • Flow Cytometry
  • Gene Transfer Techniques
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / physiopathology*
  • Mice
  • Mice, Mutant Strains
  • Milk Proteins*
  • Mutagenesis / physiology
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / physiopathology*
  • Neoplasm Transplantation
  • Oncogene Proteins, Fusion / genetics*
  • Oncostatin M
  • Peptides / genetics
  • Phenotype
  • Retroviridae / genetics
  • STAT5 Transcription Factor
  • Trans-Activators / genetics*


  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Milk Proteins
  • OSM protein, human
  • Oncogene Proteins, Fusion
  • Osm protein, mouse
  • Peptides
  • STAT5 Transcription Factor
  • Stat5a protein, mouse
  • TEL-JAK2 fusion protein, human
  • TEL-JAK2 fusion protein, mouse
  • Trans-Activators
  • Oncostatin M