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A . Sensitivity heatmap for HSP90i (17-AAG, <t>Geldanamycin</t> and Alvespimycin). Color code is representative of Z-scores (see color key at the top) calculated for each compound from IC50 values. Color code in the bottom line indicates specimen subgroups (−3/del(3p) or ctrl AML). The tree at the top depicts the unsupervised hierarchical clustering computed from IC50 values. B . Correlation plot comparing responses to 17-AAG and Alvespimycin (Pearson’s correlation coefficient r = 0.79). The dotted line results from a least squares regression. C . Response to HSP90 inhibitors for -3/del(3p) specimens vs . control AML ( left panel ), according to TP53 status ( central panel ) and ribosomal eigengene expression ( right panel , tier 1 = low expressors and tier 3 = high expressors). The average response to HSP90 inhibitors (avg(HSP90i)) corresponds to the mean value of rescaled IC50 vectors (from -1 to 1) obtained for each inhibitor. P-values resulting from the comparison between groups or conditions are indicated on the plot. D . Representative blots showing RPS14, RPL14, RPL29 and tubulin alpha (TUBA, loading control) levels as assessed by western blot analysis of total proteins extracted from U937 cells exposed to DMSO or HSP90 inhibitors (Alvespimicin, Geldanamycin and 17-AAG (1M)) for 24hrs. E . Representative blots showing RPL29 and tubulin alpha (TUBA, loading control) levels as assessed by western blot analysis of total proteins extracted from primary AML cells (samples A to D: control AML without -3/del(3p) alteration; samples E to H: -3/del(3p) AML) exposed to DMSO or HSP90 inhibitors (Alvespimicin, Geldanamycin and 17-AAG (1M)) for 24hrs. F . Correlation plots comparing RPL29 intensity (normalized on tubulin alpha, TUBA) with responses to HSP90 inhibitors. The dotted lines result from least squares regressions. The Pearson’s correlation coefficient calculated for each compound is directly indicated on the plots (top left).
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A . Sensitivity heatmap for HSP90i (17-AAG, <t>Geldanamycin</t> and Alvespimycin). Color code is representative of Z-scores (see color key at the top) calculated for each compound from IC50 values. Color code in the bottom line indicates specimen subgroups (−3/del(3p) or ctrl AML). The tree at the top depicts the unsupervised hierarchical clustering computed from IC50 values. B . Correlation plot comparing responses to 17-AAG and Alvespimycin (Pearson’s correlation coefficient r = 0.79). The dotted line results from a least squares regression. C . Response to HSP90 inhibitors for -3/del(3p) specimens vs . control AML ( left panel ), according to TP53 status ( central panel ) and ribosomal eigengene expression ( right panel , tier 1 = low expressors and tier 3 = high expressors). The average response to HSP90 inhibitors (avg(HSP90i)) corresponds to the mean value of rescaled IC50 vectors (from -1 to 1) obtained for each inhibitor. P-values resulting from the comparison between groups or conditions are indicated on the plot. D . Representative blots showing RPS14, RPL14, RPL29 and tubulin alpha (TUBA, loading control) levels as assessed by western blot analysis of total proteins extracted from U937 cells exposed to DMSO or HSP90 inhibitors (Alvespimicin, Geldanamycin and 17-AAG (1M)) for 24hrs. E . Representative blots showing RPL29 and tubulin alpha (TUBA, loading control) levels as assessed by western blot analysis of total proteins extracted from primary AML cells (samples A to D: control AML without -3/del(3p) alteration; samples E to H: -3/del(3p) AML) exposed to DMSO or HSP90 inhibitors (Alvespimicin, Geldanamycin and 17-AAG (1M)) for 24hrs. F . Correlation plots comparing RPL29 intensity (normalized on tubulin alpha, TUBA) with responses to HSP90 inhibitors. The dotted lines result from least squares regressions. The Pearson’s correlation coefficient calculated for each compound is directly indicated on the plots (top left).
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A . Sensitivity heatmap for HSP90i (17-AAG, Geldanamycin and Alvespimycin). Color code is representative of Z-scores (see color key at the top) calculated for each compound from IC50 values. Color code in the bottom line indicates specimen subgroups (−3/del(3p) or ctrl AML). The tree at the top depicts the unsupervised hierarchical clustering computed from IC50 values. B . Correlation plot comparing responses to 17-AAG and Alvespimycin (Pearson’s correlation coefficient r = 0.79). The dotted line results from a least squares regression. C . Response to HSP90 inhibitors for -3/del(3p) specimens vs . control AML ( left panel ), according to TP53 status ( central panel ) and ribosomal eigengene expression ( right panel , tier 1 = low expressors and tier 3 = high expressors). The average response to HSP90 inhibitors (avg(HSP90i)) corresponds to the mean value of rescaled IC50 vectors (from -1 to 1) obtained for each inhibitor. P-values resulting from the comparison between groups or conditions are indicated on the plot. D . Representative blots showing RPS14, RPL14, RPL29 and tubulin alpha (TUBA, loading control) levels as assessed by western blot analysis of total proteins extracted from U937 cells exposed to DMSO or HSP90 inhibitors (Alvespimicin, Geldanamycin and 17-AAG (1M)) for 24hrs. E . Representative blots showing RPL29 and tubulin alpha (TUBA, loading control) levels as assessed by western blot analysis of total proteins extracted from primary AML cells (samples A to D: control AML without -3/del(3p) alteration; samples E to H: -3/del(3p) AML) exposed to DMSO or HSP90 inhibitors (Alvespimicin, Geldanamycin and 17-AAG (1M)) for 24hrs. F . Correlation plots comparing RPL29 intensity (normalized on tubulin alpha, TUBA) with responses to HSP90 inhibitors. The dotted lines result from least squares regressions. The Pearson’s correlation coefficient calculated for each compound is directly indicated on the plots (top left).

Journal: bioRxiv

Article Title: TP53 -mutant AML with ribosomal gene loss exhibits impaired protein translation and sensitivity to HSP90 inhibition

doi: 10.1101/2025.10.01.679539

Figure Lengend Snippet: A . Sensitivity heatmap for HSP90i (17-AAG, Geldanamycin and Alvespimycin). Color code is representative of Z-scores (see color key at the top) calculated for each compound from IC50 values. Color code in the bottom line indicates specimen subgroups (−3/del(3p) or ctrl AML). The tree at the top depicts the unsupervised hierarchical clustering computed from IC50 values. B . Correlation plot comparing responses to 17-AAG and Alvespimycin (Pearson’s correlation coefficient r = 0.79). The dotted line results from a least squares regression. C . Response to HSP90 inhibitors for -3/del(3p) specimens vs . control AML ( left panel ), according to TP53 status ( central panel ) and ribosomal eigengene expression ( right panel , tier 1 = low expressors and tier 3 = high expressors). The average response to HSP90 inhibitors (avg(HSP90i)) corresponds to the mean value of rescaled IC50 vectors (from -1 to 1) obtained for each inhibitor. P-values resulting from the comparison between groups or conditions are indicated on the plot. D . Representative blots showing RPS14, RPL14, RPL29 and tubulin alpha (TUBA, loading control) levels as assessed by western blot analysis of total proteins extracted from U937 cells exposed to DMSO or HSP90 inhibitors (Alvespimicin, Geldanamycin and 17-AAG (1M)) for 24hrs. E . Representative blots showing RPL29 and tubulin alpha (TUBA, loading control) levels as assessed by western blot analysis of total proteins extracted from primary AML cells (samples A to D: control AML without -3/del(3p) alteration; samples E to H: -3/del(3p) AML) exposed to DMSO or HSP90 inhibitors (Alvespimicin, Geldanamycin and 17-AAG (1M)) for 24hrs. F . Correlation plots comparing RPL29 intensity (normalized on tubulin alpha, TUBA) with responses to HSP90 inhibitors. The dotted lines result from least squares regressions. The Pearson’s correlation coefficient calculated for each compound is directly indicated on the plots (top left).

Article Snippet: Alvespimicin (Selleckchem), Geldanamycin (MedChemExpress) and 17-AAG (MedChemExpress) were used at 1M for U937 cells and 500nM for primary specimens.

Techniques: Control, Expressing, Comparison, Western Blot