Targeting of the NR3C1 gene by 5q deletion/translocation in BPDCN. (A) Schematic representation of 5q alterations in BPDCN patients (n = 17/47), as indicated (left). aCGH image of case UPN 33 showing focal deletion of the NR3C1 gene (right). (B) Kaplan-Meier cumulative survival curves in BPDCN according to 5q alteration status (for simplicity, this is labeled del(5q) [UPNs 1, 2, 8, 12, 14, 21, 22, 24, 26, 27, 29, 31, 35, and 45] and non-del(5q) [UPNs 3, 9, 10, 16-19, 25, 27, 36, 37, and 40-42]; upper) and to NR3C1 deletion status (UPNs 1, 8, 14, 22, 24, 26, 27, 31, 35, and 45) (lower), determined by FISH or aCGH; ΔNR3C1). P values were determined by log-rank test. (C) FISH analysis of the t(3;5)(q21;q31) in the BPDCN cell line GEN2.2 (UPN 1) with chromosome 5q probes CTB-88J14 (green) and RP11-278J6 (red) (supplemental Table 2). Note a split signal for RP11-278J6 (NR3C1) on the der(3) and der(5) chromosomes. (D) Affymetrix-derived NR3C1 expression in BPDCN patients presenting del(5q) targeting NR3C1 or not. P value was determined by Wilcoxon test. (E) aCGH image showing 5q/NR3C1 deletion in DNA from a skin biopsy sample with leukemic infiltrate (UPN 22) compared with control DNA (Ctrl), and analysis in 2 BPDCN cases without 5q/NR3C1 deletion (UPNs 19 and 21). (F) Overview of immunostaining (diaminobenzidine and hematoxylin) of GCR on BPDCN dermal localization in a del(5q) case: NR3C1(+) (left) and a del(5q)/NR3C1 case: NR3C1(−) (upper right). Epidermal squamous cells showing positive nuclear staining are marked with thin gray arrows; leukemia infiltrate cells are marked with thick black arrows. A higher magnification of the clonal infiltrate in dermis of the same case as the upper right image shows mainly negative tumor cells (red arrow) and some positive cells (thick black arrow) (lower right). BM, bone marrow.