Towards personalized therapy in pediatric acute lymphoblastic leukemia: RAS mutations and prednisolone resistance

Optimization of treatment protocols and improved risk stratification have enhanced event-free survival rates in pediatric precursor-B acute lymphoblastic leukemia (BCP-ALL) up to 80%-90%. To cure the remaining 20% of patients and to reduce long-term side-effects in survivors, more personalized targeted therapy is warranted. Optimized high throughput screening has brought tailored therapy a step closer. Recently, high throughput sequencing in 187 high-risk BCP-ALL cases identified a high frequency of recurrent alterations in crucial signaling pathways. ovel targeted drugs will most likely serve as adjuvants to current chemotherapy regimens. Prednisolone has been shown to be the most pivotal in treating pediatric BCP-ALL, as in vivo and in vitro response to prednisolone is an important predictor for long-term clinical outcome, Hence, to improve clinical outcome, drugs need to be found which reverse resistance to prednisolone.