Figure 7.
Phosphoproteomic analyses of AML samples associated with specific mutations. (A) Volcano plot showing phosphorylated tyrosine sites in AML samples vs lineage-depleted bone marrow from healthy donors. P values are calculated using the Mann-Whitney U test and corrected for multiple-hypothesis testing with Benjamini-Hochberg method. Dashed red line shows P = .05. (B) Normalized abundance of selected tyrosine phosphosites with differences between AML and healthy samples, including the activating site tyrosine-546 on the phosphatase PTPN11/SHP2, the activating site tyrosine-313 on PRKCD, and the activating site tyrosine-705 on STAT3. Total protein abundance for all 3 proteins is shown as well, indicating that increased phosphorylation of these sites is not due to changes in overall protein abundance in AML samples. *P < .05 represent significantly different sites after multiple hypothesis correction as calculated in panel A. All sites were normalized to between 0 and 1 for display. (C) Volcano plot showing all phosphorylated sites in AML samples vs lineage-depleted bone marrow from healthy donors. P values are calculated using the t test and corrected for multiple-hypothesis testing with Benjamini-Hochberg method. Dashed red line shows P = .05. (D) Normalized abundance of selected phosphosites with differences between AML and healthy samples, including the serine-124 in the linker domain involved in optimal activation of AKT1 and multiple sites on DNMT3B of unknown function. Total protein abundance of AKT1 and DNMT3B are shown as well. *P < .05 after multiple-hypothesis correction as in panel C. (E) Volcano plot showing tyrosine phosphorylation sites comparing between FLT3D835-mutant AML samples and FLT3 wt AML samples as determined by 1-sided Mann-Whitney U test with multiple-hypothesis correction by Benjamin-Hochberg method. (F) Normalized abundance for each of the indicated phosphosites in the indicated patient groups. *P < .05 represents significantly different tyrosine phosphorylation sites between FLT3D835-mutant AML samples and FLT3 wt AML samples as determined in panel E. ND indicates a phosphosite was not detected in that group. Only FLT3-ITD samples with high variant allele frequency are shown. (G) Volcano plot showing differentially phosphorylated sites in samples initiated by PML-RARA (APL) vs other AML. P values are calculated using the t test and corrected for multiple-hypothesis testing with Benjamini-Hochberg method. (H) Normalized abundance of phosphorylated threonine-172 in the activation loop site on the kinase STK26 in APL vs other AML and healthy bone marrow. Total STK26 protein abundance is also shown. Normalized abundance of phosphorylation of the known activating site serine-63 on the transcription factor JUN in APL vs other AML and healthy bone marrow. Normalized abundance of JUN RNA is shown, since total JUN protein was below the limits of detection in this dataset. (I) Volcano plot showing differentially phosphorylated sites in TP53-mutant vs wt AML. P values are calculated using the t test and corrected for multiple-hypothesis testing with Benjamini-Hochberg method. (J) Abundance of the degradation related site serine-183 on TP53 and the activating site tyrosine-420 on FYN. NC, not calculable due to site being not detected in healthy samples; BM, bone marrow; ND, not detected; NS, not significant.

Phosphoproteomic analyses of AML samples associated with specific mutations. (A) Volcano plot showing phosphorylated tyrosine sites in AML samples vs lineage-depleted bone marrow from healthy donors. P values are calculated using the Mann-Whitney U test and corrected for multiple-hypothesis testing with Benjamini-Hochberg method. Dashed red line shows P = .05. (B) Normalized abundance of selected tyrosine phosphosites with differences between AML and healthy samples, including the activating site tyrosine-546 on the phosphatase PTPN11/SHP2, the activating site tyrosine-313 on PRKCD, and the activating site tyrosine-705 on STAT3. Total protein abundance for all 3 proteins is shown as well, indicating that increased phosphorylation of these sites is not due to changes in overall protein abundance in AML samples. *P < .05 represent significantly different sites after multiple hypothesis correction as calculated in panel A. All sites were normalized to between 0 and 1 for display. (C) Volcano plot showing all phosphorylated sites in AML samples vs lineage-depleted bone marrow from healthy donors. P values are calculated using the t test and corrected for multiple-hypothesis testing with Benjamini-Hochberg method. Dashed red line shows P = .05. (D) Normalized abundance of selected phosphosites with differences between AML and healthy samples, including the serine-124 in the linker domain involved in optimal activation of AKT1 and multiple sites on DNMT3B of unknown function. Total protein abundance of AKT1 and DNMT3B are shown as well. *P < .05 after multiple-hypothesis correction as in panel C. (E) Volcano plot showing tyrosine phosphorylation sites comparing between FLT3D835-mutant AML samples and FLT3 wt AML samples as determined by 1-sided Mann-Whitney U test with multiple-hypothesis correction by Benjamin-Hochberg method. (F) Normalized abundance for each of the indicated phosphosites in the indicated patient groups. *P < .05 represents significantly different tyrosine phosphorylation sites between FLT3D835-mutant AML samples and FLT3 wt AML samples as determined in panel E. ND indicates a phosphosite was not detected in that group. Only FLT3-ITD samples with high variant allele frequency are shown. (G) Volcano plot showing differentially phosphorylated sites in samples initiated by PML-RARA (APL) vs other AML. P values are calculated using the t test and corrected for multiple-hypothesis testing with Benjamini-Hochberg method. (H) Normalized abundance of phosphorylated threonine-172 in the activation loop site on the kinase STK26 in APL vs other AML and healthy bone marrow. Total STK26 protein abundance is also shown. Normalized abundance of phosphorylation of the known activating site serine-63 on the transcription factor JUN in APL vs other AML and healthy bone marrow. Normalized abundance of JUN RNA is shown, since total JUN protein was below the limits of detection in this dataset. (I) Volcano plot showing differentially phosphorylated sites in TP53-mutant vs wt AML. P values are calculated using the t test and corrected for multiple-hypothesis testing with Benjamini-Hochberg method. (J) Abundance of the degradation related site serine-183 on TP53 and the activating site tyrosine-420 on FYN. NC, not calculable due to site being not detected in healthy samples; BM, bone marrow; ND, not detected; NS, not significant.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal