IRF4 as an Oncogenic Biomarker for Hematological Malignancies

The lymphocyte-specific transcription factor Interferon (IFN) Regulatory Factor 4 (IRF4) is crucial for lymphocyte development. Importantly, IRF4 has potent oncogenic and transforming properties, and its intimate interaction with lymphoid and myeloid malignancies has been increasingly recognized. In general, IRF4 exerts its function by transcriptionally regulating a pool of genes pivotal for cell development, oncogenesis and immune response. In clinical practice, IRF4 serves as an important prognosis and diagnosis marker for certain types of these malignancies. However, the oncogenic roles of IRF4 in most types of these malignancies and the molecular mechanisms underlying its interaction with them are largely not characterized. Accumulating evidence from cell culture shows that IRF4 regulates differential targets in distinct cancer contexts, depending on the“context-specific”co-regulator(s) associated with it in each setting. These complementary studies with in vitro cell culture systems are a necessary strategy which will provide molecular and mechanistic insights into the specific regulation and function of IRF4 in distinct cancer contexts, and may identify novel interventions specifically targeting IRF4 regulatory network for treatment. This review summarizes the evidence obtained from bench to bed showing the association of IRF4 with various types of hematological malignancies, with emphasis on molecular mechanisms underlying its regulation and its roles in these contexts.