In this study, we aim to profile IRF4-associated unique molecular signatures in different types of hematological malignancies, by analyzing existing gene expression profile databases obtained from clinical samples. Results show that IRF4 is overexpressed in melanoma, in addition to previously reported myeoloma, lymphoma, and leukemia, and that IRF4 is associated with a unique gene expression pattern in each of these settings. Some of these genes are known IRF4 transcriptional targets, whereas some others may represent a new group of IRF4 targets. We have Ozagrel sodium verified LIMD1 and CFLAR as two novel genes whose expression is correlated with IRF4 in non-Hodgkin lymphomas, and shown that CFLAR is likely an IRF4 target. Moreover, we have profiled the IRF4 transcriptome in EBV latency by using Microarray analysis and further confirmed a panel of genes including IFI27, IFI44, GBP1, and ARHGAP18 as novel IRF4 targets. We initially checked the expression levels of IRF4 in different cancer cell lines. To this end, the gene expression data, obtained from 917 cell lines in a previous study, was analyzed at Oncomine. As shown in Fig. 1A, in 18 selected cancer types, the expression level of IRF4 was the highest in myeloma, followed by lymphoma, melanoma and leukemia. Metaproterenol Sulfate overexpression of IRF4 has been well documented in all these cancers but only a few publications have reported the association between IRF4 genetic variants or abnormal expression and skin cancer. Our results have confirmed the overexpression of IRF4 in melanoma and supported the claim that IRF4 may play an important role in the development of this cancer. For melanoma, we analyzed the dataset which includes 28 cutaneous melanoma patient samples. Top 20 genes/probes correlated with IRF4 are shown in Fig. 2C, and top 60 genes/ probes are shown in Table S1. Among these genes, the transcription factor MITF, the pigmentation enzyme TYR, and MLANA and GPR143 that are involved in melanosome biogenesis, are important players in melanoma. MITF is known to cooperate with IRF4 in regulation of the expression of TYR in melanocytes. Similar results were obtained from another dataset.