Figure 2.
Resistance to CSF1R inhibitor is associated with adverse prognostic risk gene mutations and cytogenetic abnormalities. (A) GW-2580 AUC from primary AML patient samples (n = 315) was compared for a multitude of clinical and genetic characteristics, with number of samples with evaluable data and the P value listed for each characteristic. Prognostic risk was determined using the ELN guidelines for AML (see Döhner et al51 ). The presence/absence of translocations was determined from karyotype. Only translocations that were found in ≥2 patients were considered. Mutational data were collected by either targeted sequencing, whole-exome sequencing, or targeted polymerase chain reaction (PCR)-based methods (FLT3-ITD and NPM1). Significance was determined using either Mann-Whitney or Kruskal-Wallis tests (for categorical variables) or Spearman rank correlation (for continuous variables), and corrected for multiple comparisons if applicable. (B) GW-2580 AUC among the patient population with clinical data (n = 202 samples from 199 patients), subdivided into de novo (n = 158), secondary (n = 24), and relapsed (n = 20) AML disease presentation categories. Statistics were calculated on subdivided categories by the Kruskal-Wallis test with the Dunn multiple comparisons test. (C) Kaplan-Meier survival curve of patients with AML with both clinical and survival data (n = 173), grouped by the response of their corresponding ex vivo primary sample to GW-2580: sensitive (0-20th percentile), indeterminate (20th-80th), and resistant (80th-100th). P value obtained from the overall log-rank test.