Transcriptomics

Dataset Information

3

Combination of ABT-869 with SAHA on AML with FLT3-ITD


ABSTRACT: For the microarray experiments, MV4-11 and MOLM-14 cells were treated with DMSO control, ABT-869 3 nM, SAHA 6 M and combination therapy for 24 hours. Cells were then washed in PBS and high-quality total RNA was extracted RNeasy Midi Kit, according to the manufacturer’s instruction (Qiagen, Valencia, USA). RNA quantity, quality, and purity were assessed with the use of the RNA 6000 Nano assay on the Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara CA, USA). Gene expression profiling was performed using Affymetric U133plus2.0 gene chip (Affymetrix, Santa Clara, CA, USA) according to the manufacturer’s protocol. MV4-11 and MOLM-14 cells were treated with DMSO control, ABT-869, SAHA or combination therapy for 24 hours.

ORGANISM(S): Homo sapiens  

SUBMITTER: Jianbiao Zhou   Wee-Joo Chng  Chien-Shing Chen 

PROVIDER: E-GEOD-26114 | ArrayExpress | 2011-05-31

SECONDARY ACCESSION(S): GSE26114PRJNA135197

REPOSITORIES: GEO, ArrayExpress

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Publications

PRL-3, a metastasis associated tyrosine phosphatase, is involved in FLT3-ITD signaling and implicated in anti-AML therapy.

Zhou Jianbiao J   Bi Chonglei C   Chng Wee-Joo WJ   Cheong Lip-Lee LL   Liu Shaw-Cheng SC   Mahara Sylvia S   Tay Kian-Ghee KG   Zeng Qi Q   Li Jie J   Guo Ke K   Tan Cheng Peow Bobby CP   Yu Hanry H   Albert Daniel H DH   Chen Chien-Shing CS  

PloS one 20110512 5


Combination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic. We demonstrated that combining ABT-869, a FLT3 inhibitor, with SAHA, a HDAC inhibitor, led to synergistic killing of the AML cells with FLT3 mutations and suppression of colony formation. We identified a core gene signature that is uniquely induced by the combination treatment in 2 different leukemia cell lines. Among these, we showed that downregulation o  ...[more]

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