Page 277 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR AB
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Figure 1. Proteomic profiling distinguishes TCF3::HLF+ and TCF3::PBX1+ leukemia and uncovers therapeutic vulnerabilities for both sub- types. Unsupervised hier- archical clustering (A), prin- cipal component analysis (PCA) (B) and gene set en- richment analysis (GSEA) (C) was performed on the pro- teomic data of 6 TCF3::HLF+ (in red) and 5 TCF3::PBX1+ (in orange) B-cell acute lym- phoblastic leukemia (B-ALL) patient-derived xenograft samples. For unsupervised hierarchical clustering, the 10% most variable proteins were used based on the standard deviation. PCA was performed on all proteins. Both subtypes clearly seg- regate into distinct clusters suggesting highly distinct proteomic landscapes. (C) GSEA is based on all pro- teins and identifies several gene sets enriched in either of the two subgroups. (D) Proteomic data shows en- richment of MYC protein expression in TCF3::HLF+ versus TCF3::PBX1+ leukemic samples in this study. In or- der to determine differential expression, non-parametric Mann-Whitney t test (two- tailed) was used. (E) Gene set enrichment plot of MYC targets showing a positive correlation with TCF3::HLF+ leukemia.
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