Primary CLL cells characterized with ex vivo high-throughput drug screening platform.
Drug library consisted of 67 compounds at different concentrations.
Micro-environmental conditions mimicked by heat inactivated human serum.
CLL samples: untreated, sensitive or refractory disease and major genetic subgroups.
Cell viability assessed 48 and 72 hours after drug application.
Drug sensitivity regressed on genetic profiles.
Results reported from 97 primary CLL samples.
Nutlin-3a and fludarabine: induced cell death with wild-type p53 (n=80) but considerably less in CLL with mutated p53.
Inhibitors with related targets showed similar response profiles across patients.
Drug effects can be based on functional and genetic properties of tumors.
CLL functional classification based on drug sensitivity.
TP53 mutant CLL: identifies synthetic lethal interaction.