title: Inhibition of STAT5: a therapeutic option in BCR-ABL1-driven leukemia.
abstract: The two transcription factors STAT5A and STAT5B are central signaling molecules in leukemias driven by Abelson fusion tyrosine kinases and they fulfill all criteria of drug targets. STAT5A and STAT5B display unique nuclear shuttling mechanisms and they have a key role in resistance of leukemic cells against treatment with tyrosine kinase inhibitors (TKI). Moreover, STAT5A and STAT5B promote survival of leukemic stem cells. We here discuss the possibility of targeting up-stream kinases with TKI, direct STAT5 inhibition via SH2 domain obstruction and blocking nuclear translocation of STAT5. All discussed options will result in a stop of STAT5 transport to the nucleus to block STAT5-mediated transcriptional activity. In summary, recently described shuttling functions of STAT5 are discussed as potentially druggable pathways in leukemias.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Berger
authors.affiliation: Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Sexl
authors.affiliation: Department of Medicine I, Division of Hematology and Ludwig-Boltzmann Cluster Oncology, Medical University of Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Ludwig-Boltzmann Institute for Cancer Research, University of Veterinary Medicine, Medical University Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
mesh_terms: D000818:Animals; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D050799:STAT5 Transcription Factor