[HTML][HTML] Stat5 tetramer formation is associated with leukemogenesis

R Moriggl, V Sexl, L Kenner, C Duntsch, K Stangl… - Cancer cell, 2005 - cell.com
R Moriggl, V Sexl, L Kenner, C Duntsch, K Stangl, S Gingras, A Hoffmeyer, A Bauer
Cancer cell, 2005cell.com
Activation of Stat5 is frequently found in leukemias. To study the mechanism and role of
Stat5 activation, we introduced a constitutively activated Stat5a mutant, cS5 F, into murine
bone marrow (BM) cells. BM transplantation with cS5 F-transfected cells caused
development of multilineage leukemias in lethally irradiated wild-type or nonirradiated
Rag2−/− mice. The leukemic cells showed strongly enhanced levels of cS5 F tetramers but
unchanged cS5 F dimer levels in a DNA binding assay. Moreover, Stat5a mutants …
Abstract
Activation of Stat5 is frequently found in leukemias. To study the mechanism and role of Stat5 activation, we introduced a constitutively activated Stat5a mutant, cS5F, into murine bone marrow (BM) cells. BM transplantation with cS5F-transfected cells caused development of multilineage leukemias in lethally irradiated wild-type or nonirradiated Rag2−/− mice. The leukemic cells showed strongly enhanced levels of cS5F tetramers but unchanged cS5F dimer levels in a DNA binding assay. Moreover, Stat5a mutants engineered to form only dimers, but not tetramers, failed to induce leukemias. In addition, Stat5 tetramers were found to accumulate in excess compared to dimers in various human leukemias. These data suggest that Stat5 tetramers are associated with leukemogenesis.
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