Drug Sensitivity patterns across FAB subtypes and molecular mutations in AML: A comprehensive analysis for precision medicine

Background

Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by distinct French–American–British (FAB) classifications and molecular mutations. Understanding how these biological markers relate to drug responses is crucial for refining therapeutic approaches.

Methods

We examined drug sensitivity patterns in 186 AML patients using selective Drug Sensitivity Scores (sDSS), analysing data from 515 commercially available chemotherapeutic and targeted oncology agents. Drug sensitivity was analysed across various FAB subtypes (M0, M1, M2, M4, M4 eos, M4/M5, and M5) and important mutations (NPM1, FLT3, FLT3-ITD, FLT3-TKD and KIT).

Results

Navitoclax showed greater effectiveness in M0, M1, and M2 subtypes. NPM1 mutations were linked to increased sensitivity to multiple therapeutic agents. FLT3-ITD mutations were associated with significant responsiveness to PI3K/mTOR inhibitors. Analysis of drug combinations revealed complexities in using multiple therapeutic agents, often leading to reduced effectiveness but providing insights into successful drug pairings.

Conclusions

The findings underscore the necessity for personalised therapeutic strategies in AML, advocating for treatment protocols that integrate individual mutation profiles and FAB classifications to enhance patient care and improve clinical outcomes.