Nona Struyf

Abstract Clinical implementation of patient cell-based drug testing is hampered by inconsistencies and irreproducible results. Using linear mixed models and drug response data from four cohorts of patients with acute myeloid leukemia (n = 993 samples), we identified sources of variability in ex vivo drug sensitivity testing across the studies.

Abstract FLT3-mutated acute myeloid leukemia (AML) remains difficult to treat due to frequent resistance to FLT3 inhibitors like midostaurin. In this study, we observed a progenitor-like CD38+CD45RA+ leukemic cell population that may be associated with midostaurin resistance. Midostaurin-resistant cells display disrupted membrane architecture and a shift in signaling from STAT5 to PI3K/AKT, favoring survival over apoptosis.

Abstract Consistent handling of samples is crucial for achieving reproducible molecular and functional testing results in translational research. Here, we used 229 acute myeloid leukemia (AML) patient samples to assess the impact of sample handling on high-throughput functional drug testing, mass spectrometry-based proteomics, and flow cytometry. Our data revealed novel and previously described changes in cell phenotype and drug response dependent on sample biobanking.