![Figure 1. A BPDCN-specific transcriptomic signature with a dysregulation of genes involved in cholesterol homeostasis allows the clustering of BPDCN samples. (A) A schematic representation of cellular cholesterol homeostasis. Mechanisms of cholesterol synthesis and uptake (green boxes) and efflux (blue box) maintain cellular cholesterol homeostasis. The LXR pathway is involved in the regulation of cholesterol homeostasis by inhibiting cholesterol uptake/entry (through the decreased expression of low-density lipoprotein (LDL) and/or very-low-density lipoprotein (VLDL) receptors, LDLR and VLDLR, respectively) and by stimulating cholesterol efflux (through ABC transporters, ABCA1 and ABCG1). This LXR pathway is activated by intermediates from the mevalonate pathway (ie, the cholesterol biosynthesis). Cholesterol efflux also requires cholesterol acceptors, APOA1/APOE, and HDL2/3 to form mature HDL. These cholesterol acceptors can be provided by the cell itself or represent circulating apolipoproteins or lipoprotein particles. Molecules used to modify cholesterol homeostasis in BPDCN are indicated in blue font. (B) Transcriptomic analysis of 65 AML, 35 T-ALL, and 12 BPDCN samples (highlighted in red, right side of the panel) was performed using an Affymetrix U133-2 chip and dChip software. (C) Transcriptomic analysis of the 12 BPDCN samples was compared with 5 primary PDC samples obtained using an Affymetrix U133-2 chip and dChip software. (D) Basal LXR target gene (ABCA1, ABCG1) transcripts were quantified by qRT-PCR in 2 established BPDCN cell lines, CAL-1 (n = 7) and GEN2.2 cells (n = 4), as well as in a short-term BPDCN cell line, BES1 (n = 3) and 4 primary BPDCN samples (leukemic PDC [LPDC] #2-4, and #7, n = 1). Levels of mRNA were normalized to those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for each sample and then expressed as fold change relative to the average value for normal PDCs. Results from n independent experiments with each symbol representing an experiment (*P < .05, **P < .01, ****P < .0001, Mann-Whitney). FASN, fatty acid synthase; RXR, retinoid X receptor.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/128/23/10.1182_blood-2016-06-724807/4/blood724807f1.jpeg?Expires=1724942536&Signature=3w~HwwpCCBOKfldJwCRZWi-SgUU9B0Y4OcSZJVyq~hiefuS2QfTk3OjSPHa8g-PnpkNh4MzM~yaIpI1qYsw39SQzca5IWscDVEi8~fwvHw77ApBYPa~A1M4FjonfCtZIodw85WcDO-Cro01vQ8Hdsz8d9Rv3-SP3cDquOSvH5cUklx2gJ0Z83CYkPFmz8qRsrxZaKcIViFI-9HIq0A9Z7R6NgBD~w5GC63dcyrmN8IaD6uw4bczgIcNnvqy-fyZgPDd2OtkyToHAxaWfH-WvkHF5QEV4ERgg~tHfNqtvQVJ4YP8hX5U~pa7Jz2lXgCpVjzR216OzxYf2zapCsDV~Uw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
A BPDCN-specific transcriptomic signature with a dysregulation of genes involved in cholesterol homeostasis allows the clustering of BPDCN samples. (A) A schematic representation of cellular cholesterol homeostasis. Mechanisms of cholesterol synthesis and uptake (green boxes) and efflux (blue box) maintain cellular cholesterol homeostasis. The LXR pathway is involved in the regulation of cholesterol homeostasis by inhibiting cholesterol uptake/entry (through the decreased expression of low-density lipoprotein (LDL) and/or very-low-density lipoprotein (VLDL) receptors, LDLR and VLDLR, respectively) and by stimulating cholesterol efflux (through ABC transporters, ABCA1 and ABCG1). This LXR pathway is activated by intermediates from the mevalonate pathway (ie, the cholesterol biosynthesis). Cholesterol efflux also requires cholesterol acceptors, APOA1/APOE, and HDL2/3 to form mature HDL. These cholesterol acceptors can be provided by the cell itself or represent circulating apolipoproteins or lipoprotein particles. Molecules used to modify cholesterol homeostasis in BPDCN are indicated in blue font. (B) Transcriptomic analysis of 65 AML, 35 T-ALL, and 12 BPDCN samples (highlighted in red, right side of the panel) was performed using an Affymetrix U133-2 chip and dChip software. (C) Transcriptomic analysis of the 12 BPDCN samples was compared with 5 primary PDC samples obtained using an Affymetrix U133-2 chip and dChip software. (D) Basal LXR target gene (ABCA1, ABCG1) transcripts were quantified by qRT-PCR in 2 established BPDCN cell lines, CAL-1 (n = 7) and GEN2.2 cells (n = 4), as well as in a short-term BPDCN cell line, BES1 (n = 3) and 4 primary BPDCN samples (leukemic PDC [LPDC] #2-4, and #7, n = 1). Levels of mRNA were normalized to those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for each sample and then expressed as fold change relative to the average value for normal PDCs. Results from n independent experiments with each symbol representing an experiment (*P < .05, **P < .01, ****P < .0001, Mann-Whitney). FASN, fatty acid synthase; RXR, retinoid X receptor.
