MDM2-SNP 309 allele status does not affect sensitivity to MDM2 inhibitors in CLL

We appreciate the rationale for testing MDM2 single nucleotide polymorphism (SNP) 309 status in chronic lymphocytic leukemia (CLL) as a potential predictor of sensitivity to murine double minute 2 (MDM2) inhibitor treatment and for progressive CLL¹  as outlined in the letter to the editor by Seyfried et al. We did indeed test our published cohort of CLL cases for SNP309 status using genomic polymerase chain reaction on DNA derived from fluorescence-activated cell sorted CD19⁺ cells.²  In total, 87 samples without known p53 aberrations (wt p53 exon 5-9 sequence and preserved p53 induction in response to MDM2 inhibitor treatment) were genotyped.

As demonstrated in Figure 1, we found no association between MDM2 inhibitor concentration that resulted in 50% apoptosis (IC₅₀ values) and MDM2-SNP309 genotype (allele status TT, TG, or GG). Thus, based on this data in CLL, MDM2 protein levels do not seem to affect MDM2 inhibitor sensitivity.