Project description:KMT2A-rearranged (KMT2A-R)- leukemia is a distinct and rare form of leukemia which mostly affects children. Despite extensive research, KMT2A-R-patients have a dismal prognosis and no targeted therapy is yet available in the clinics. SET is a potent oncoprotein and an endogenous inhibitor of the phosphatase PP2A. In this study we show that SET is specifically enriched in KMT2A-R-leukemic stem cells (LSCs) and it is essential for the self-renewal of KMT2A-R-cells. Treatment with SET-PP2A inhibitor FTY720 disrupted SET-PP2A interaction leading to cell cycle arrest, cellular death and increased sensitivity to chemotherapy treatment in KMT2A-R-models. Genetic and pharmacological inhibition of SET via FTY720 led to down-regulation in the expression of several genes belonging to the KMT2A-R-leukemia signature, including MYC, HOXA10 and HOXA9/MEIS1 target genes. Taken together these results demonstrated that SET represents an interesting and novel player of KMT2A-R-leukemia and its antagonism through FTY720 could serve as a novel strategy to treat this disease.
Project description:Expression data from untreated or Dll4-Fc treated THP1 cell line. We used Dll4-Fc stimulation of AML cells to study whether Notch activation has an impact on AML. We analyzed THP1 cell line in vitro treated with Dll4-Fc or vehicle control to determine genes affected by Notch activation.
Project description:Expression data from untreated or Dll4-Fc treated THP1 cell line. We used Dll4-Fc stimulation of AML cells to study whether Notch activation has an impact on AML. We analyzed THP1 cell line in vitro treated with Dll4-Fc or vehicle control to determine genes affected by Notch activation. THP1 cell line was cultured on plate coated with 30 nM Dll4-Fc or vehicle for 48 hours prior to RNA extraction and hybridization to Human Genome U133 Plus 2.0 Affymetrix arrays.
Project description:CRISPR Cas9 guided knockout (KO) of PHF6 in human THP1 AML cell line. We performed bulk RNA-Seq on knockout (PHF6 KO) and wildtype (CTRL) clones derived from THP1 cells transduced with lentiviral vectors encoding Cas9 protein and either PHF6 gRNAs or non-targeting gRNAs. Our results reveal that PHF6 knockout upregulates self-renewal gene sets and downregulates myeloid differentiation gene sets.
Project description:We report the use of complementary peptide antigen enrichment and comprehensive mass spectrometric acquisition strategies to provide in-depth immunopeptidome data for AML cell line THP1
Project description:We report the use of complementary peptide antigen enrichment and comprehensive mass spectrometric acquisition strategies to provide in-depth immunopeptidome data for AML cell line THP1
Project description:The histone methyltransferases DOT1L (H3K79me1,2,3 KMT, "activating" chromatin mark) and EZH2 (H3K27me1,2,3 KMT, "silencing" mark) have both been shown to be required for growth and survival of KMT2A rearranged AML cells. Both KMTs have been shown to modulate expression of HOXA cluster genes, albeit for EZH2 this has not been shown in the context of KMT2A rearranged AML, but in other subtypes of AML. We asked what transcriptional effects dual inhibition of DOT1L and EZH2 has in KMT2A rearranged AML.
Project description:The histone methyltransferases DOT1L (H3K79me1,2,3 KMT, "activating" chromatin mark) and EZH2 (H3K27me1,2,3 KMT, "silencing" mark) have both been shown to be required for growth and survival of KMT2A rearranged AML cells. Both KMTs have been shown to modulate expression of HOXA cluster genes, albeit for EZH2 this has not been shown in the context of KMT2A rearranged AML, but in other subtypes of AML. We asked what transcriptional effects dual inhibition of DOT1L and EZH2 has in KMT2A rearranged AML.