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Transcription profiling of human T-ALL cell lines treated with DMSO or SAHM1

ABSTRACT: NOTCH proteins regulate signaling pathways involved in cellular differentiation, proliferation and death. Overactive Notch signaling as been observed in numerous cancers and has been extensively studied in the context of T-cell acute lymphoblastic leukemia (T-ALL) where more than 50% of pateints harbour mutant NOTCH1. Small molecule modulators of these proteins would be important for understanding the role of NOTCH proteins in malignant and normal biological processes. We were interested to measure the global changes in gene expression upon treatment of the human T-ALL cell lines HPB-ALL and KOPT-K1 with either vehicle alone (DMSO) or SAHM1, an alpha-helical hydrocarbon stapled peptide derived from the MAML1 co-activator protein. Experiment Overall Design: Triplicate cultures of KOPT-K1 or HPB-ALL cells were treated with either DMSO alone or SAHM1 (20 uM) for 24 hours. Total RNA was extracted and hybridized to Affymetrix human U133 plus 2.0 microarrays (three arrays per treatment per cell line for a total of 12 arrays).

ORGANISM(S): Homo sapiens

SUBMITTER: Raymond Moellering

PROVIDER: E-GEOD-18198 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Expression profile of human T-ALL cell lines treated with DMSO or SAHM1

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Transcription profiling of mouse lymphoblasts from animals treated with vehicle or SAHM1

Project description:NOTCH proteins regulate signaling pathways involved in cellular differentiation, proliferation and death. Overactive Notch signaling as been observed in numerous cancers and has been extensively studied in the context of T-cell acute lymphoblastic leukemia (T-ALL) where more than 50% of pateints harbour mutant NOTCH1. Small molecule modulators of these proteins would be important for understanding the role of NOTCH proteins in malignant and normal biological processes. We were interested to measure the global gene expression changes in leukemic cells isolated from mice harbouring a NOTCH1-driven genetically engineered T-cell leukemia after treatment with SAHM1, a synthetically stabilized Î±-helical peptide derived from the MAML1 co-activator protein. Experiment Overall Design: A genetically engineered murine model of NOTCH1-driven T-ALL was developed by retroviral transduction of murine bone marrow with a mutant NOTCH1 allele commonly observed in human T-ALL patients. Transplantation of transduced cells gave rise to T-ALL that was quantifiable by bio-luminescence in our model. After established leukemia was evident by continually increased tumor burden (luminescence) mice were either treated with vehicle alone (5% DMSO in Hank's buffered saline solution) or SAHM1 (30 mg/kg, twice daily, intraperitoneal injection). After five days of treatment, mice receiving SAHM1 had a significant decrease in tumor growth. To measure a pharmacodynamic effect on Notch signaling, circulating lymphoblasts were collected from vehicle- (n=3) and SAHM1-treated (n=3) mice and gene expression profiles were generated.

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Targeting of the NOTCH transcription complex by a novel small molecule inhibitor CB-103 in KOPT-K1 cells

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Expression data from U373 cells expressing EGFP, MAML1-dn and DTX1-myc

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Gene expression profiles of T-cell acute lymphoblastic leukemia cell lines with and without chronic GSI-treatment

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