Figure 4.
Figure 4. HGF stimulates growth in CSF1R inhibitor–sensitive samples and its secretion is regulated by CSF1R activation. (A) Schematic of analysis connecting cytokine growth assay results (data from Carey et al32) with CSF1R inhibitor sensitivity. (B) Cytokines and growth factors that increase AML cell growth are significantly associated with sensitivity to GW-2580. Data represent log2 fold change of GW-2580 AUCs between responders and nonresponders (n = 68 primary AML patient samples and 94 cytokines/growth factors) vs the unadjusted P value, determined by Student t tests. (C) Schematic of evaluating cytokine secretion after stimulation/inhibition of CSF1R in primary AML patient samples (n = 15). (D-E) Change in cytokine levels in conditioned media of primary AML patient samples after (D) CSF1R stimulation and (E) CSF1R inhibition. Cytokine levels for each patient sample are normalized to untreated and ranked by median value. (F) Difference in rank order of cytokines from panels D and E identifies cytokine secretion profile associated with upregulated and downregulated CSF1R activity. (G) Baseline HGF levels in primary AML patient samples correlate with GW-2580 sensitivity (n = 10). Significance determined by Spearman rank correlation.

HGF stimulates growth in CSF1R inhibitor–sensitive samples and its secretion is regulated by CSF1R activation. (A) Schematic of analysis connecting cytokine growth assay results (data from Carey et al32 ) with CSF1R inhibitor sensitivity. (B) Cytokines and growth factors that increase AML cell growth are significantly associated with sensitivity to GW-2580. Data represent log2 fold change of GW-2580 AUCs between responders and nonresponders (n = 68 primary AML patient samples and 94 cytokines/growth factors) vs the unadjusted P value, determined by Student t tests. (C) Schematic of evaluating cytokine secretion after stimulation/inhibition of CSF1R in primary AML patient samples (n = 15). (D-E) Change in cytokine levels in conditioned media of primary AML patient samples after (D) CSF1R stimulation and (E) CSF1R inhibition. Cytokine levels for each patient sample are normalized to untreated and ranked by median value. (F) Difference in rank order of cytokines from panels D and E identifies cytokine secretion profile associated with upregulated and downregulated CSF1R activity. (G) Baseline HGF levels in primary AML patient samples correlate with GW-2580 sensitivity (n = 10). Significance determined by Spearman rank correlation.

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