Schwaller J, Parganas E, Wang D, Cain D, Aster J C, Williams I R, Lee C K, Gerthner R, Kitamura T, Frantsve J, Anastasiadou E, Loh M L, Levy D E, Ihle J N, Gilliland D G
Division of Hematology and Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
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.
信号转导和转录激活因子5（STAT5）在多种人类血液系统恶性肿瘤中被激活。我们采用遗传学方法探讨了STAT5激活对于由TEL/JAK2诱导的骨髓增殖性和淋巴增殖性疾病是否必要。用表达TEL/JAK2的逆转录病毒转导骨髓移植的小鼠会发展出迅速致命的骨髓增殖性和淋巴增殖性综合征，而用表达TEL/JAK2的Stat5ab缺陷小鼠来源的骨髓进行重建则不会诱发疾病。在Stat5a/b缺陷背景下的疾病诱导通过编码TEL/JAK2和Stat5a的双顺反子逆转录病毒得以挽救。此外，用表达组成型活性突变体Stat5a或单一Stat5a靶点——小鼠抑瘤素M（mOSM）的骨髓细胞进行重建可诱导骨髓增殖性疾病。这些数据确定了Stat5a/b和mOSM在TEL/JAK2疾病发病机制中的关键作用。
