title: Ikaros expression sensitizes leukemic cells to the chemotherapeutic drug doxorubicin.
abstract: Ikaros is an important transcription factor involved in the development and differentiation of hematopoietic cells. However, its role in the treatment of hematopoietic malignancies such as leukemia is less well understood. In the present study, it was observed by data mining of the Oncomine database that high expression levels of full-length Ikaros (IK1) is correlated with increased sensitivity of cancer cells to treatments with chemotherapeutic drugs, including doxorubicin (DOX). To examine the functional significance of this observation, the expression of IK1 in a leukemia cell line was altered, and the response of leukemic cells to DOX treatment was analyzed. It was observed that overexpression of IK1 could enhance DOX-induced apoptosis, while knockdown of IK1 attenuated DOX-induced apoptosis in leukemic cells. Further experiments demonstrated that IK1 sensitized leukemic cells to DOX-induced apoptosis, probably through upregulation of caspase-9. These data suggest that high expression levels of IK1 may be a potential biomarker to predict responses of leukemia patients to treatment with chemotherapy.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Laboratory Medical and Life Science, Wenzhou Medical University, Chashan Higher Education Park, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Licai
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Internal Medicine, Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Shenmeng
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Laboratory Medical and Life Science, Wenzhou Medical University, Chashan Higher Education Park, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Laboratory Medical and Life Science, Wenzhou Medical University, Chashan Higher Education Park, Wenzhou, Zhejiang 325035, P.R. China.
authors.forename: Shang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Laboratory Medical and Life Science, Wenzhou Medical University, Chashan Higher Education Park, Wenzhou, Zhejiang 325035, P.R. China; Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Haihua
authors.initials: H
authors.lastname: Gu
keywords: Ikaros; apoptosis; caspase-9; doxorubicin; leukemia