PRL2 Promotes Leukemogenesis through Inhibiting the p53 Tumor Suppressor Signaling Pathway in Leukemia-initiating Cells

MLL-rearranged (MLL-r) acute myeloid leukemia (AML) is an aggressive subtype of leukemia characterized by poor prognosis, frequent relapse, and resistance to conventional therapies. These challenges highlight the urgent need for novel therapeutic targets. The phosphatase of regenerating liver (PRL) family proteins, also known as protein tyrosine phosphatase 4A (PTP4A), have been identified as oncoproteins in various human cancers. Among the three PRL family members (PRL1, PRL2, and PRL3), PRL2/PTP4A2 has been shown to play important roles in both normal and malignant hematopoiesis. Previous study found that PRL2 is highly expressed in MLL-r AML, but its role in leukemogenesis remains poorly understood. To understand how PRL2 promotes MLL-AF9-driven AML, we performed RNA-Seq analysis to compare gene expressions in PRL2+/+ and PRL2-/- LICs expressing MLL-AF9. Comparative analysis revealed significant changes in gene expression associated with p53 pathway activation upon PRL2 loss. This dataset provides a valuable resource for understanding the molecular mechanisms underlying PRL2 function in MLL-r AML and may support future efforts to identify novel therapeutic targets.