The PIK3CA/PIK3CD mRNA ratio can predict resistance to GS-1101. (A) Gene expression of class IA PI3K isoforms, relative to GAPDH, in 12 diagnostic MCL PBMCs and 3 healthy B-cell controls, showing significant increase in PIK3CA and PIK3CD compared with controls (gray) and very low levels of PIK3CB. (B) A PIK3CA/PIK3CD greater than twice the mean ratio in healthy B cells identifies a subset of primary samples (5/12) that are resistant to 0.1 µM and 1 µM GS-1101 (GS), but show significantly higher toxicity with equimolar concentrations of GDC-0941 (GDC). (C) This cutoff, when applied to an independent validation cohort (n = 10), was able to identify GS-1101–resistant samples (primary samples treated with 1 μM of GS-1101 and GDC-0941).