Figure 4.

IGF1R expression is associated with unmutated IGHV status and trisomy 12 in human CLL. (A) Western blot analysis for IGF1R, p-AKT, and p-ERK levels in A20 cells overexpressing Igf1r compared with empty vector–transduced cells. (B) Dose-response curve for analyzing sensitivity of Igf1r-overexpressing or empty vector–transduced A20 cells to GS-649443 in vitro using an MTS assay. The P value was calculated using the extra-sum-of-squares F test comparing the best-fit values between the 2 curves. (C) Gene-expression profiling and unsupervised clustering of RTKs in a cohort of 337 previously untreated CLL patient samples identified 2 major clusters distinguished based on high and low levels of IGF1R. A subcluster with lower IGF1R and higher FGFR1 was also observed. (D) Association of IGF1R expression with hierarchical genomic aberration subgroups (with the exception of trisomy 12). (E) Correlation of IGF1R expression with gene mutations. (F) IGF1R expression in cases with and without trisomy 12 within the IGHV subgroups. P values in (D-F) were calculated using the Mann-Whitney U test. (G) Overview of IGF1R and FGFR1 expression with various genetic subgroups in CLL. Among the clusters, orange refers to cluster 1 and blue refers to cluster 2 in Figure 4C. High IGF1R (>median) is shown in red, and low IGF1R (≤median) is shown in green. Heat map with log2 ratios of IGF1R expression shown with a color scale of red (high expression) to green (low expression). Incidence of 17p deletion (17p-), 11q deletion (11q-), normal karyotype, and 13q deletion (13q-) represent the hierarchical model. ns, not statistically significant. *P ≤ .05; ***P ≤ .001; ns, P > .05.