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

STATE is activated in a broad spectrum of human hematologic malignancies. W e addressed whether STATE activation is necessary for the myelo- and lympho proliferative disease induced by TEL/JAK2 using a genetic approach. Whereas mice transplanted with bone marrow transduced with retrovirus expressing T EL/JAK2 develop a rapidly fatal myelo- and lymphoproliferative syndrome, re constitution with bone marrow derived from Stat5ab-deficient mice expressin g TEL/JAK2 did not induce disease. Disease induction in the Stat5a/b-defici ent background was rescued with a bicistronic retrovirus encoding TEL/JAK2 and Stat5a. Furthermore, myeloproliferative disease was induced by reconsti tution with bone marrow cells expressing a constitutively active mutant, St at5a, or a single Stat5a target, murine oncostatin M (mOSM). These data def ine a critical role for Stat5a/b and mOSM in the pathogenesis of TEL/JAK2 d isease.