Ex vivo AML patient sample screen reveals that knockdown/inhibition of CSF1R reduces leukemia cell survival in >20% of samples. (A) Schematic of screening primary AML patient samples against small-molecule inhibitors and siRNAs against the tyrosine kinome to identify new therapeutic targets. (B) siRNA tyrosine kinome screen (n = 93 kinase siRNAs) identifies CSF1R as the top “hit” in primary AML patient samples (n = 158 or 162) to significantly reduce cell viability. (C) High degree of specificity among the CSF1R-targeted small-molecule inhibitors GW-2580, ARRY-382, and JNJ-28312141, compared with other class III receptor tyrosine kinases. Data from (1) Davis et al³⁵  and (2) Wright et al.³⁶  (D) Strong correlation observed between GW-2580 AUC and z score of the viability from siCSF1R compared with that of other tyrosine kinase siRNAs (n = 162 patient samples). Significance determined by Spearman rank correlation. (E) siCSF1R has the strongest correlation and most significant association with GW-2580 AUC in the siRNA tyrosine kinome screen. Slope of linear regression line calculated for each siRNA as indicated in panel D was plotted against the P value, determined by significance test for linear regression. (F) Profile of sensitivity to GW-2580 across the cohort of primary AML patient samples (n = 315). The relative positions of representative dose-response curves (G-H) are indicated. (G-H) Representative dose-response curves for a (G) sensitive and (H) nonsensitive primary AML patient sample to GW-2580.