Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/16573
Title: In vitro and in vivo study of ABT-869 in treatment acute myeloid leukemia (AML) alone or in combination with chemotherapy or HDAC inhibitors: insight into molecular mechanism and biologic characterization
Authors: ZHOU JIANBIAO
Keywords: acute myeloid leukemia, FLT3, ABT-869, HDAC inhibitor, chemotherapy, resistance
Issue Date: 26-Feb-2009
Source: ZHOU JIANBIAO (2009-02-26). In vitro and in vivo study of ABT-869 in treatment acute myeloid leukemia (AML) alone or in combination with chemotherapy or HDAC inhibitors: insight into molecular mechanism and biologic characterization. ScholarBank@NUS Repository.
Abstract: Internal tandem duplications (ITDs) of fms-like tyrosine kinase 3 (FLT3) receptor play an important role in the pathogenesis of AML and represent an attractive therapeutic target. We first demonstrate ABT-869, a multi-targeted receptor tyrosine kinase inhibitor (TKI) as a potent FLT3 inhibitor. ABT-869 demonstrates significant sequence dependent synergism with cytarabine and doxorubicin. Low density array (LDA) analysis revealed the synergistic interaction involved in down-regulation of cell cycle and MAPK pathway genes. ABT-869 also reduced the FLT3 wide type leukemia burden and prolonged survival. Next we discovered that enhanced activation of STAT pathways and overexpression of survivin are the main mechanism of resistance to ABT-869, suggesting potential targets for reducing resistance developed in patients receiving FLT3 inhibitors.We demonstrated that combining ABT-869 with SAHA leaded to synergistic killing of AML cells with FLT3 mutations. Our results suggest such combination therapies may significantly improve the therapeutic efficacy of FLT3 inhibitors in clinic.
URI: http://scholarbank.nus.edu.sg/handle/10635/16573
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Ph.D. Thesis_Zhou Jianbiao_Department of Medicine, NUS_Oct 09.pdf3.05 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

249
checked on Dec 18, 2017

Download(s)

565
checked on Dec 18, 2017

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.