Figure 5.
TRMT5 function and predictive value in leukemia. (A) Quantification (left) and representative engraftment images (right) of xenotransplanted Ctr and TRMT5-KO cells (OCI-AML2) into host mice. (B) Leukemia-free survival of mice transplanted with Ctr and KO OCI-AML2 (left) or KO MOLM13 (right) cells at the indicated time points. (C) Illustration of AML patient cohort and treatment. (D) Gene set enrichment analyses (GSEA) for genes encoding proteins regulating mitochondrial translation (top) and the ETC (bottom) using RNA expression levels of AraC treatment-responsive patients with leukemia at the time of diagnosis (n = 12) revealing complete remission (Rem) after first induction therapy. (E-F) Heat map of log2 RNA normalized counts (ClustVis) (E) and z-score (F) of gene regulation–encoding proteins of the ETC (WP111; n = 86) in non-responders (non-resp) (n = 20), intermediate responders (n = 47), and patients having complete Rem (n = 12) at first induction therapy. (G) Average log2 FC of normalized RNA counts of ETC genes (WP111) in patients not responding to therapy (n = 20) compared with patients having complete Rem (n = 12). (H-I) Prediction of survival of all patients with AML (n = 734) (H) or patients treated with chemotherapy (n = 79) (I) (kmplot.com) using the average expression of the 8 most downregulated WP111 genes in non-resp in G (blue bars): 218563_at (NDUFA3), 223112_s_at (NDUFB10), 203606_at (NDUFS6), 202839_s_at (NDUFB7), 208998_at (SLC25A8), 203190_at (NDUFS8), and 213041_s_at (ATP5D). Only JetSet probes were used. (J-K) Illustration (J) and overlap of significantly (P < .05) differently abundant proteins (K) of AML patient samples collected for proteomics analysis.20 (L-M) Percentage of proteins (n = 80) in panel K localizing to mitochondria (MitoCarta3.0) (L) and GSEA analysis (https://tau.cmmt.ubc.ca/eVITTA/) revealing significantly (P < .05) enriched pathways in relapsed adult and pediatric (pediat.). AML samples (M). Šídák multiple comparisons test (panel F). HR, hazard ratio; NES, normalized enrichment score.

TRMT5 function and predictive value in leukemia. (A) Quantification (left) and representative engraftment images (right) of xenotransplanted Ctr and TRMT5-KO cells (OCI-AML2) into host mice. (B) Leukemia-free survival of mice transplanted with Ctr and KO OCI-AML2 (left) or KO MOLM13 (right) cells at the indicated time points. (C) Illustration of AML patient cohort and treatment. (D) Gene set enrichment analyses (GSEA) for genes encoding proteins regulating mitochondrial translation (top) and the ETC (bottom) using RNA expression levels of AraC treatment-responsive patients with leukemia at the time of diagnosis (n = 12) revealing complete remission (Rem) after first induction therapy. (E-F) Heat map of log2 RNA normalized counts (ClustVis) (E) and z-score (F) of gene regulation–encoding proteins of the ETC (WP111; n = 86) in non-responders (non-resp) (n = 20), intermediate responders (n = 47), and patients having complete Rem (n = 12) at first induction therapy. (G) Average log2 FC of normalized RNA counts of ETC genes (WP111) in patients not responding to therapy (n = 20) compared with patients having complete Rem (n = 12). (H-I) Prediction of survival of all patients with AML (n = 734) (H) or patients treated with chemotherapy (n = 79) (I) (kmplot.com) using the average expression of the 8 most downregulated WP111 genes in non-resp in G (blue bars): 218563_at (NDUFA3), 223112_s_at (NDUFB10), 203606_at (NDUFS6), 202839_s_at (NDUFB7), 208998_at (SLC25A8), 203190_at (NDUFS8), and 213041_s_at (ATP5D). Only JetSet probes were used. (J-K) Illustration (J) and overlap of significantly (P < .05) differently abundant proteins (K) of AML patient samples collected for proteomics analysis.20 (L-M) Percentage of proteins (n = 80) in panel K localizing to mitochondria (MitoCarta3.0) (L) and GSEA analysis (https://tau.cmmt.ubc.ca/eVITTA/) revealing significantly (P < .05) enriched pathways in relapsed adult and pediatric (pediat.). AML samples (M). Šídák multiple comparisons test (panel F). HR, hazard ratio; NES, normalized enrichment score.

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