B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is the most common childhood cancer. It is a highly heterogeneous malignant hematological disorder that is driven by recurrent genetic abnormalities. Hence, the molecular genetic makeup of BCP-ALL influences treatment strategies and dictates risk stratification. GATA3 is a T-cell lineage transcription factor where its expression is tightly regulated during normal development of lymphoid progenitors. We discovered that significant elevated expression of GATA3 is a distinct feature of the 8-11% of BCP-ALL cases that harbor ZNF384, MEF2D and DUX4 fusion oncogenes. We hypothesize that aberrant expression of GATA3 is a unifying secondary genetic lesion in the pathogenesis of these BCP-ALL subsets that have different clinical and biological characteristics. Hence, in this proposal, we aim to gain a deeper understanding of the role of GATA3 misexpression across these subsets. Ultimately, we hope this will improve the current classification of BCP-ALL and uncover potential therapeutic targets.