Fig. 1: SET is an oncogene over-expressed in acute myeloid leukemia.
From: SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML
A Hierarchical tree plot that shows the expression of SET mRNA in human HSCs, progenitors and differentiated blood cells. The level of expression is visualized by size and color of the nodes (data obtained from Bloodspot Gene expression profiles (GSE42519); n = 34; hematopoietic stem cells (HSC) n = 4, multipotential progenitors (MPP) n = 2, common myeloid progenitors (CMP) n = 3, granulocyte myeloid progenitors (GMP) n = 5, megakaryocyte-erythroid progenitor cells (MEP) n = 2, early promyelocyte (ea_PM) n = 3, late promyelocyte (late_PM) n = 3, myelocyte (MY) n = 2, metamyelocyte (MM) n = 3, band cell (BC) n = 4, polymorphonuclear cells n = 3. B Heatmap of SET mRNA along with other oncogenes, housekeeping genes and genes annotated as either down-regulated or up-regulated in KMT2A-R leukemia in a large AML- RNAseq dataset (n = 384) comprising 31 samples from patients carrying rearrangements of KMT2A. Meta-analyses of RNAseq data from Leucegene (GSE62190, GSE66917, GSE67039). 1: complex karyotype, 2: EVI-R; 3: intermediate; 4: inversion 16; 5: KMT2A-R; 6: monosomy 5; 7 normal karyotype; 8: t(15:17); 9: t(8;21); 10 trisomy-tetrasomy 8. C Kaplan–Meier analysis showing the survival in AML patients with low (n = 106) or high expression levels of SET (n = 57). Meta-analyses of micro-array data from the PrognoScan database (GSE12417). Log-Rank test; *p < 0.05. D, E Immunoblot of SET in KMT2A-R- AML cell lines (MV411, THP1, ML2, MLOM13, NOMO1), KMT2A-R-ALL cell lines (SEM, HB11;19, KOPN8, RS4;11), KMT2A-R-primary samples (PS) and six independent healthy bone marrow (BM) controls. The data also present the expression of SET in three KMT2A-wt cell lines K562 (BCR::ABL (t19;22) erythroleukemia cell line, Kasumi1 (AML1:ETO, t8;21 AML cell line) and U937 (CALM::AF10, AML cell line). Densitometry analysis was conducted by Li-COR Image Studio software. GAPDH was used as a loading control. Values are expressed as ratio between SET and GAPDH, relative to the expression of SET in mononuclear cells isolated from bone marrow of healthy volunteers (BM). F Immunoblot of SET in cytoplasmic and nuclear factions of KMT2A-wt (K562) and KMT2A-R-AML cell lines (THP1 and MV411). Laminin B1 and GAPDH were used as nuclear and cytoplasmic markers, respectively. G Detection of SerSET in KMT2A-R cell lines. Immunoblotting against phosphorylated Ser was performed after SET immunoprecipitation.
