Gene expression overlap affects karyotype prediction in pediatric acute lymphoblastic leukemia

Leukemia is the most common childhood malignancy in the United States. Acute lymphoblastic leukemia (ALL) accounts for 75% of new leukemia cases in children. Although the outcome for children with ALL has improved dramatically over the past three decades, 25% of children with ALL still develop recurrent disease. Current risk classification schemes in pediatric ALL use clinical and laboratory parameters such as age and initial white blood cell count, as well as the presence of specific ALL-associated cytogenetic or molecular genetic abnormalities. Stratification based on cytogenetic analysis and molecular genetic detection consider B precursor ALL translocations such as t(12;21)(TEL-AML1), t(1;19)(E2A-PBX1) and t(9;22)(BCR-ABL), as well as numerical imbalances such as hyperdiploidy, specific chromosome trisomies or hypodiploidy. Despite such efforts, current diagnosis and risk classification schemes in pediatric ALL remain imprecise. In particular, it is likely that a significant number of higher-risk children are currently overtreated and could be cured with less intensive regimens, resulting in fewer toxicities and long-term side effects. Finally and conversely, a significant number of children in lower-risk categories still relapse and precise means to prospectively identify them have remained elusive.