Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2.
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.
Schwaller
J
J
Division of Hematology and Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Parganas
E
E
Wang
D
D
Cain
D
D
Aster
J C
JC
Williams
I R
IR
Lee
C K
CK
Gerthner
R
R
Kitamura
T
T
Frantsve
J
J
Anastasiadou
E
E
Loh
M L
ML
Levy
D E
DE
Ihle
J N
JN
Gilliland
D G
DG
D000818:Animals; D015139:Blotting, Southern; D001854:Bone Marrow Cells / Q000473:pathology; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005355:Fibrosis; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D008894:Milk Proteins; D016296:Mutagenesis / Q000502:physiology; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000503:physiopathology*; D009368:Neoplasm Transplantation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D053683:Oncostatin M; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D012190:Retroviridae / Q000235:genetics; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000235:genetics*; D053614:Janus Kinase 2; D000097764:ETS Translocation Variant 6 Protein
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D015514:Oncogene Proteins, Fusion; D053683:Oncostatin M; D010455:Peptides; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; C508351:OSM protein, human; C508352:Osm protein, mouse; C494093:Stat5a protein, mouse; C108603:TEL-JAK2 fusion protein, human; D053614:Janus Kinase 2; D000097764:ETS Translocation Variant 6 Protein; C491568:TEL-JAK2 fusion protein, mouse