github link
Accession IconGSE144638

Expression data from human AML cell lines

Organism Icon Homo sapiens
Sample Icon 14 Downloadable Samples
Technology Badge Icon Affymetrix Clariom S Human array (clariomshuman)

Submitter Supplied Information

Description
Pediatric Acute Myeloid Leukemia (AML) is an aggressive and poor prognosis malignancy for which there are few effective targeted approaches, despite the numerous genetic alterations, including MLL gene rearrangements (MLL-r). The histone methyltransferase DOT1L is involved in supporting proliferation of MLL-r cells, for which a target inhibitor, Pinometostat, has been evaluated in a clinical trial recruiting pediatric MLL-r leukemic patients. However, modest clinical effects have been reported. Recent studies reported that additional leukemia subtypes lacking MLL-r are sensitive to DOT1L inhibition. Here we report that targeting DOT1L with Pinometostat sensitizes pediatric AML cells to further treatment with the multi-kinase inhibitor Sorafenib, irrespectively of MLL-r. DOT1L pharmacologic inhibition induces AML cell differentiation and modulated expression of genes with relevant roles in cancer development. Such modifications in transcriptional program impact on further treatments, inducing a strong sensitization to Sorafenib, with increased apoptosis and growth suppression of both AML cell lines and primary pediatric AML cells with diverse genotypes. We used microarrays to define differential regulation of gene expression in AML cell lines with or without MLL gene rearrangements following pharmacologic inhibition of DOT1L.
PubMed ID
Total Samples
28
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Treatment
Processing Information
Additional Metadata
No rows found
Loading...