Fig. 1
From: Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia
Immunoproteasome function is a vulnerability in KMT2A-r AML. A GO enrichment analysis on MS-based global proteome analysis on murine LSC-enriched GFP+ c-Kit+ cells of KMT2A::MLLT3-induced leukemia compared to AML1-ETO9a (n = 4). Displayed are the Top 30 GO-terms (“molecular function”) sorted by p-value. B Gene expression of catalytic proteasome subunits in hematopoietic stem cells (HSC), KMT2A-r leukemia (AML t(11q23)/KMT2A) or non-KMT2A-r AML (AML other) (https://servers.binf.ku.dk/bloodspot/). The box-and-whisker plots display the 90/10 percentiles at the whiskers, the 75/25 percentiles at the boxes, and the median. Mann–Whitney U test was performed. C Protein abundance of catalytic immunoproteasome subunit PSMB8 in KMT2A-r (blue) or non-KMT2A-r (black) AML cell lines (https://depmap.org/portal/). D Growth curves depicting cell counting after trypan blue exclusion of MOLM-13, THP-1, MONO-MAC-6, KOPN-8 and ML-2 cells transduced with shRNAs targeting PSMB8 or a non-targeting control (shNT). n = 3–5 independent experiments, in triplicate; mean with Standard Error of Mean (SEM); 2-way ANOVA. E Cell numbers on day 10; plating of 2.5 × 102 MOLM-13 or ML-2 cells in methylcellulose. n = 3 independent experiments; mean with Standard Deviation (SD); paired Student t test. F Kaplan–Meier survival curves of NSGS recipient mice transplanted with 1 × 105 MOLM-13 or ML-2 cells, expressing PSMB8-shRNA2 (n = 9 for MOLM-13; n = 8 for ML-2) and -shRNA3 (n = 6; n = 7) or non-targeting control (shNT: n = 9; n = 9); two independent cohorts; Mantel-Cox test