Genetic Alterations In Childhood Acute Lymphoblastic Leukemia: Interactions With Clinical Features And Treatment Response

Simple Summary The latest molecular taxonomy of acute lymphoblastic leukemia (ALL) comprises >20 distinct genetic subtypes, each with their own unique clinical and prognostic characteristics. In this review, we describe how these new genetic subtypes interact with clinical presenting features, IKZF1(del), treatment response, and outcomes, which is helpful for clinical use. Acute lymphoblastic leukemia (ALL) is the most common cancer among children. This aggressive cancer comprises multiple molecular subtypes, each harboring a distinct constellation of somatic, and to a lesser extent, inherited genetic alterations. With recent advances in genomic analyses such as next-generation sequencing techniques, we can now clearly identify >20 different genetic subtypes in ALL. Clinically, identifying these genetic subtypes will better refine risk stratification and determine the optimal intensity of therapy for each patient. Underpinning each genetic subtype are unique clinical and therapeutic characteristics, such as age and presenting white blood cell (WBC) count. More importantly, within each genetic subtype, there is much less variability in treatment response and survival outcomes compared with current risk factors such as National Cancer Institute (NCI) criteria. We review how this new taxonomy of genetic subtypes in childhood ALL interacts with clinical risk factors used widely, i.e., age, presenting WBC, IKZF1(del), treatment response, and outcomes.