Warburg metabolic states are heterogeneous and frequent in pediatric hematological malignancies

Background: Enhanced aerobic glycolysis in cancer is commonly known as the Warburg effect. Clinically, Warburg metabolism has been associated with poor prognosis and therapy resistance in multiple cancer types, and this metabolic shift has been well-documented in adult cancer patients. Nevertheless, combined data regarding the presence, clinical implications and molecular features of the Warburg effect in pediatric oncology remain scarce. Methods: Here, we assessed the incidence and heterogeneity of Warburg metabolism and investigated 15 pediatric hematological cancer samples using various approaches including bioenergetic profiling. Results: Based on three initial cases of childhood cancer presenting with hyperlactatemia in peripheral blood despite sufficient oxygen availability, we aimed to identify Warburg effects in hematological cancer during clinical practice. Based on functional analyses, we found that Warburg parameters were present in > 70% of the assessed samples (10 out of 14 cases) derived from pediatric hematological cancer patients. There was no overall correlation between cellular ATP production sources and the mRNA expression of essential glycolytic genes. Furthemore, cellular hexokinase 2 (HK2) protein quantity but not transcription level correlated with the Warburg status. Conclusions: Hence, we highlight the importance of determining parameters related to the Warburg effect as a relevant marker in pediatric hematological malignancies, which could strengthen the understanding of cancer cell metabolism in children and improve anti-cancer treatment efficiency by specifically targeting Warburg metabolism.