Aim 1: Enroll childhood leukemia patients with banked cord blood, then sequence leukemia specimens to determine the driving molecular lesions in each patient, followed by backtracking in cord blood using patient-specific droplet digital PCR (ddPCR) assays to determine which leukemia subtypes arise prenatally and their clonal frequency across cord blood cell compartments. Aim 2: Investigate the cell-of-origin of leukemia-initiating lesions and transcriptomic changes from pre-leukemia to overt leukemia, across childhood leukemia subtypes, at the single-cell level using TARGET-Seq in paired cord blood and diagnostic leukemia samples. Aim 3: To determine whether the presence and frequency of pre-leukemic clones correlate with leukemia risk factors, including demographic, pre/perinatal, and genomic risk factors for ALL/AML. Created with BioRender.com.