E-MTAB-1817 - Transcription profiling by array of human erythroleukemic (HEL) cell line treated with TG101209, an inhibitor of Janus kinase 2 (JAK2) and the BET inhibitor, GSK1210151A (I-BET151)

Status
Released on 20 August 2013, last updated on 3 June 2014
Organism
Homo sapiens
Samples (12)
Array (1)
Protocols (7)
Description
Small molecule inhibition of the BET family of proteins, which bind acetylated lysines within histones, has been shown to have a marked therapeutic benefit in pre-clinical models of MLL-fusion protein driven leukemias. Here, we report that I-BET151, a highly specific BET family bromodomain inhibitor, leads to growth inhibition in a human erythroleukemic (HEL) cell line as well as in erythroid precursors isolated from polycythemia vera patients. One of the genes most highly down regulated by I-BET151 was LMO2, an important oncogenic regulator of hematopoietic stem cell development and erythropoiesis. We previously reported that LMO2 transcription is dependent upon JAK2 kinase activity in HEL cells. Here, we show that the transcriptional changes induced by a JAK2 inhibitor (TG101209) and I-BET151 in HEL cells are significantly over-lapping, suggesting a common pathway of action. We generated JAK2 inhibitor resistant HEL cells and showed that these retain sensitivity to I-BET151. These data highlight I-BET151 as a potential alternative treatment against myeloproliferative neoplasms driven by constitutively active JAK2 kinase.
Experiment types
transcription profiling by array, co-expression, compound treatment design, in vitro
Contacts
Citation
BET Protein Inhibition shows Efficacy Against JAK2V617F-Driven Neoplasms. Wyspianka B., Bannister AJ, Barbieri I, Nangalia J, Godfrey A, Calero-Nieto FJ, Robson SC, Rioja I, Li J, Wiesse M, Cannizzaro E, Dawson MA, Huntly B, Prinjha RK, Green AR, Gottgens B, Kouzarides T.
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-MTAB-1817.idf.txt
Sample and data relationshipE-MTAB-1817.sdrf.txt
Raw data (1)E-MTAB-1817.raw.1.zip
Processed data (1)E-MTAB-1817.processed.1.zip
Array designA-MEXP-2072.adf.txt
Links