Project description:Acute myeloid leukemia (AML) represents 20% of pediatric leukemia, but accounts for most of disease-related mortality in children, due to chemo-resistance or relapse. Treatment modalities tailored according to specific AML genetic subgroups are critically needed to improve survival and decrease morbidity. To address this need we report here the results of a small molecule screen that was performed using 12,000 compounds using human leukemia models, matched patient diagnostic and relapse samples, and cell lines. As part of this work, expression profiling was performed in order to correlate drug response to gene expression differences between samples.
Project description:Acute myeloid leukemia (AML) represents 20% of pediatric leukemia, but accounts for most of disease-related mortality in children, due to chemo-resistance or relapse. Treatment modalities tailored according to specific AML genetic subgroups are critically needed to improve survival and decrease morbidity. To address this need we report here the results of a small molecule screen that was performed using 12,000 compounds using human leukemia models, matched patient diagnostic and relapse samples, and cell lines. As part of this work, expression profiling was performed in order to correlate drug response to gene expression differences between samples.
Project description:We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. This SuperSeries is composed of the following subset Series:; GSE976: Gene Expression-Based High Throughput Screening: APL Treatment with Candidate Compounds; GSE982: Gene Expression-Based High Throughput Screening: HL-60 Cell Treatment with Candidate Compounds; GSE983: Gene Expression-Based High Throughput Screening: Primary Patient AML Blasts, Normal Neutrophils, and Normal Monocytes; GSE985: Gene Expression-Based High Throughput Screening: HL-60 Cells Treated with ATRA and PMA Experiment Overall Design: Refer to individual Series
Project description:We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. This SuperSeries is composed of the SubSeries listed below.
Project description:Label-free quantitation dataset from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls including 3 lineage-depleted and 3 CD34+ selected bone marrows.
Project description:Expression profiles of acute myeloid leukemia patient samples. Blasts and mononuclear cells were purified from bone marrow or peripheral blood aspirates of acute myeloid patients. Samples contained 80-100 percent blast cells. Total RNA was extracted by lyses with guanidium isothiocyanate followed by cesium chloride gradient purification
Project description:Expression profiles of acute myeloid leukemia patient samples. Blasts and mononuclear cells were purified from bone marrow or peripheral blood aspirates of acute myeloid patients. Samples contained 80-100 percent blast cells. Total RNA was extracted by lyses with guanidium isothiocyanate followed by cesium chloride gradient purification Keywords: other
Project description:A deep-scale proteome and phosphoproteome database from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls including 3 lineage-depleted and 3 CD34+ selected bone marrows.
Project description:Cure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted. golub-00392 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG-U133A, HG-U133A_2 Organism: Homo sapiens (ncbitax) Material Types: cell, total_RNA, synthetic_RNA, organism_part, whole_organism*Cell Types: Disease States: Acute Myeloid Leukemia, Normal, Acute Myeloid Leukemia