B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients?

SIMPLE SUMMARY: B-ALL is the more frequent childhood malignancy. Even though significant improvements in patients’ survival, some pediatric B-ALL have still poor prognosis and novel strategies are needed. Recently, new genetic abnormalities and altered signaling pathways have been described, defining novel B-ALL subtypes.Innovative targeted therapeutic drugs may potentially show a great impact on the treatment of B-ALL subtypes, offering an important chance to block multiple signaling pathways and potentially improving the clinical management of B-ALL younger patients, especially for the new identified subtypes that lack efficient chemotherapeutic protocols. In this review, we shed light on the up-to-date knowledge of the novel childhood B-ALL subtypes and the altered signaling pathways that could become new druggable targets. ABSTRACT: B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic malignancy that arises from the clonal expansion of transformed B-cell precursors and predominately affects childhood. Even though significant progresses have been made in the treatment of B-ALL, pediatric patients’ outcome has to be furtherly increased and alternative targeted treatment strategies are required for younger patients. Over the last decade, novel approaches have been used to understand the genomic landscape and the complexity of the molecular biology of pediatric B-ALL, mainly next generation sequencing, offering important insights into new B-ALL subtypes, altered pathways, and therapeutic targets that may lead to improved risk stratification and treatments. Here, we will highlight the up-to-date knowledge of the novel B-ALL subtypes in childhood, with particular emphasis on altered signaling pathways. In addition, we will discuss the targeted therapies that showed promising results for the treatment of the different B-ALL subtypes.