Browse
Submit Data
Databases
API
Help

Dataset Information

346 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MZH29 is a novel potent FLT3 tyrosine kinase inhibitor with activity of overcoming drug resistant mutations in AML

ABSTRACT: In this study, we screened a group of newly synthesized tyrosine kinase inhibitors, and discovered MZH29 was a potent FLT3 inhibitor. Remarkably, MZH29 is well tolerated and effective in the clinically known FLT3 mutants in the constructed BaF3 model cells. MZH29 could also lead to complete tumor regression in the mouse xenograft model and increases survival in the bone marrow engraftment model. Further proteomics study indicates that the inhibition effects of MZH29 and AC220 are in a similar manner. All the results present here support that MZH29 could be a promising candidate for both the FLT3 WT and drug resistance mutant AML.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Apis Mellifera (honeybee)

TISSUE(S): Monocyte, Cell Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Wei Ge

LAB HEAD: Wei Ge

PROVIDER: PXD004278 | Pride | 2016-12-12

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

MZH29 is a novel potent inhibitor that overcomes drug resistance FLT3 mutations in acute myeloid leukemia.

Xu B B Zhao Y Y Wang X X Gong P P Ge W W

Leukemia 20161024 4

More than one-third of patients with acute myeloid leukemia (AML) harbor aberrant mutations in Fms-like tyrosine kinase 3 (FLT3). Among them, the internal tandem duplication (ITD) mutation predicts poor prognosis. MZH29 is a novel FLT3 inhibitor synthesized in our laboratory that showed that cellular and kinase assays sustained inhibitory effects on wild-type and mutant FLT3, including the FLT3-ITD, FLT3-D835H/Y/V and FLT3-K663Q mutants. More importantly, MZH29 retained its potent inhibitory eff ...[more]

PMID: 27773927

Similar Datasets

Next generation sequencing identifies small RNA expression in FLT3-ITD+ AML (MV4-11) cell lines

Project description:The expression level of microRNAs in FLT3-ITD+ AML is unknown. Using empty vector (EV) lentiviral CRISPR-Cas9 infected FLT3-ITD+ AML cell lines (MV4-11 cells), we performed next generation RNA sequencing on small RNAs to determine microRNA expression level in these cells. We found a variety of evolutionarily conserved and non-conserved microRNAs expressed in our cells of interest. Small RNAseq on EV lentiviral CRISPR-Cas9 infected MV4-11 cell lines was performed on triplicate cultures.

2016-07-01 | E-GEOD-71543 | biostudies-arrayexpress

Expression profile of wild type (WT) vs miR-155-/- in FLT3-ITD+ AML (MV4-11) cell lines

Project description:The expression profile in miR-155-/- FLT3-ITD+ AML is unknown. Using empty vector (EV) or two distinct miR-155 (S3 or S10) lentiviral CRISPR-Cas9 infected FLT3-ITD+ AML cell lines (MV4-11 cells), we performed next generation RNA sequencing to determine the expression profile in these cells dependent on miR-155. We found a number of pathways dysregulated, including STAT5 activation. RNAseq was performed on EV or miR-155 lentiviral CRISPR-Cas9 infected MV4-11 cell lines in triplicate cultures.

2016-07-01 | E-GEOD-71541 | biostudies-arrayexpress

Comparation the mRNA Expression Profile of the MV4-11 Sorafenib Resistant Cells and the Parental Cells

Project description:Our gene set analysis of MV4-11-R versus MV4-11 indicated decreased depolarization of mitochondria and mitochondrial membrane, mitochondrial dysfunction and anti-apoptosis as other top ranked molecular or cellular functions of differential gene sets. expression of most genes encoding glycolytic enzymes was up-regulated in MV4-11-R cells we revealed a metabolic alteration in sorafenib-resistant cell lines with mitochondrial respiration deficiency, leading to substantial decrease of mitochondria-derived ATP generation and a significant increase in glycolytic activity to maintain sufficient ATP production. Our study revealed a metabolic signature of sorafenib resistance and indicated that increase of glycolytic activity including upregulation of major glycolytic enzymes may be viewed as a marker for early detection of sorafenib resistance in AML patients with FLT3/ITD mutation and glycolytic inhibitors warrant further investigation as alternative therapeutic agents for sorafenib-resistant cells Sorafenib resistant cells MV411-R VS. parental MV4-11 cells. Biological replicates: 3 control replicates, 3 treated replicates.

2016-08-01 | E-GEOD-74666 | biostudies-arrayexpress

Transcription profiling of human AML cell lines treated with rapamycin treatment - evidence for Skp2 and p27 mediated G1 arrest

Project description:Acute Myelod Leukaemia cells were treated with specific dosages of the drug rapamycin and RNA was extracted. The RNA was then hybridised onto Affymetric HG U133A chips.

2009-12-25 | E-MEXP-2170 | biostudies-arrayexpress

Genome-wide CRISPR-Cas9 screen identifies protein-coding genes and microRNAs important in FLT3-ITD+ AML (MV4-11) cellular growth

Project description:The functional relevance of many microRNAs in the context of tumor biology remains unclear. Using CRISPR-Cas9 technology, we performed a global loss-of-function screen to test the impact of individual microRNAs on the growth of FLT3-ITD positive leukemia cells. This approach identified both evolutionarily conserved and non-conserved human microRNAs that function to suppress or promote tumor cell growth, revealing that microRNAs are extensively integrated into the molecular networks that control tumor cell physiology. Our study describes a powerful genetic approach by which the function of individual microRNAs can be assessed on a global level, and its use will rapidly advance our understanding of how microRNAs contribute to human disease. Loss-of-function CRISPR-Cas9 screen identifies genes whose loss leads to increased or decreased FLT3-ITD+ cell growth over 23 day time-course

2016-07-01 | E-GEOD-71539 | biostudies-arrayexpress

Chemical translatome analysis in AML cells treated with different drug combinations

Project description:Our prior research has shown that AML with FLT3-ITD is particularly susceptible to the combination of FLT3 inhibitors and protein synthesis inhibitors when compared to FLT3-WT. In this study, we employed a click chemistry-based approach to quantify the alterations in the translatome under FLT3 inhibition and protein synthesis inhibition in AML cells.

2024-03-26 | PXD047567 | Pride

Transcription profiling of rat at pheochromocytoma cell line PC12 treated with trimethyltin at low and high doses

Project description:The rat pheochromocytoma cell line PC12 cells were cultured in complete DMEM till 80% confluence, then placed at 5000 cells per squared cm. Cells were then plated in 24-well plates for cell viability assay and in T75 flasks for RNA isolation. Medium was replaced with serum-free fresh medium for 12 hours prior to TMT treatment. Gene expression patterns were then analysed using Rat Expression Array 230A Experiment Overall Design: In this study we analize gene expression patterns in PC12 cells treated with Trimethyltin (TMT). We utilized control cells (untreated) and two different concentration (1 and 5) Experiment Overall Design: We used three biological replicates, for the three concentration tested, according to MIAME guidelines Experiment Overall Design: (total 9 chips were used in this study).

2009-04-29 | E-GEOD-5073 | biostudies-arrayexpress

Microarray analysis of the effects of a Î³-tocopherol-rich mixture of tocopherols on global gene expression in the prostates of TRAMP mice

Project description:We used whole mouse genome microarrays to the effects of Î³-TmT on global gene expression in the prostate TRAMP and age-matched C57BL/6 mice were administered either 600 mg/kg of Î³-TmT or a control vehicle via oral gavage. Twelve hours after dosing, prostate tissues were collected for RNA extraction.

2014-09-16 | E-GEOD-61416 | biostudies-arrayexpress

Global ChIP-seq Normalization Reveals Epigenome Modulations

Project description:Epigenomic profiling by ChIP-seq is a prevailing methodology used to investigate chromatin-based regulation in biological systems, such as human disease, yet the lack of an empirical methodology to normalize amongst experiments has limited the usefulness of this technique. Here we describe a “spike-in” normalization method that allows the quantitative comparison of histone modification status across cell populations using defined quantities of a reference epigenome. We demonstrate the utility of this method in measuring epigenomic changes following chemical perturbations and show how control normalization of ChIP-seq experiments enables discovery of disease-relevant changes in histone modification occupancy. ChIP-Seq of histone modifications H3K79me2 and H3K4me3 in human samples treated with EPZ-5676 with/without reference epigenome spike-in.

2014-10-30 | E-GEOD-60104 | biostudies-arrayexpress

JAK2 Naive and Persitent Murine BaF3 cells infected with MPLW515L

Project description:Transcriptional profiling of Murine BaF3 cells infected with MPLW515L grown under either normal conditions (Naive) or in 0.8 uM INCB18424 for 4-6 weeks (Persistent). Naive and Persistent cells were then treated with either DMSO (Control) or 0.8 uM INCB18424 for 4 hours. Goal was to determine transcriptional changes conditioned upon sensitivity/resistance of BaF3 MPLW515L mutants to JAK1/2 specific inhibitor. 3 condition experiment consiting of: 1) Naive cells treated with DMSO (Control) , 2) Naïve cells treated with 0.8 uM INCB18424 for 4 hours (Acute) and 3) Persistent cells treated with 0.8 uM INCB18424 for 4 hours (Persistent). Biological replicates: 3 DMSO control replicates, 3 Acute replicates, 3 Persistent replicates.

2012-05-30 | E-GEOD-38335 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data