IRF-4 Suppresses BCR/ABL Transformation of Myeloid Cells in a DNA Binding-independent Manner

Abstract

Background: IRF-4 functions both as an oncoprotein and as a tumor suppressor in different cell context. Results: We found that IRF-4 inhibits BCR/ABL transformation of myeloid cells independent of its DNA binding and nuclear localization. Conclusion:The oncogenic and tumor suppressor functions of IRF-4 involve distinct pathways. Significance: The studies help to develop improved therapies for malignancies involving IRF-4.

Accelerated Development of Chronic Lymphocytic Leukemia in New Zealand Black Mice Expressing a Low Level of Interferon Regulatory Factor 4

“…These findings indicate that high levels of IRF4 inhibit the survival of CLL cells through means that are independent of its role as a transcriptional regulator. It is worth noting that our finding is in line with a recent study that shows that IRF4, without its DNA binding domain, can still suppress BCR/ABL (Abelson tyrosine kinase) oncogene-induced myeloid leukemia (49). Their analysis further shows that it is the C-terminal IRF ϩ/Ϫ CLL clones as well as three independent NZB IRF4 ϩ/ϩ B1 cells were used for Western blot analysis.…”

“…Because the DNA binding domain of IRF4 contains a nuclear localization signal, the truncated IRF4 is localized predominantly in the cytosol (49,50). How cytosolic IRF4 suppresses Akt activity remains unclear.…”

Dual mechanisms by which miR-125b represses IRF4 to induce myeloid and B-cell leukemias

“…Indeed, multiple studies have recently demonstrated that deletion of IRF4 in mice leads to the development of B-cell leukemia. [12][13][14][26][27][28][29] …”

The EBV Latent Antigen 3C Inhibits Apoptosis through Targeted Regulation of Interferon Regulatory Factors 4 and 8

“…More recently studies have indicated that IRF4, when overexpressed, functions as an oncoprotein [27]. On the contrary, IRF4 was found down-regulated in some myeloid and early B-lymphoid malignancies [28], and so IRF4 may have different functions in the context of different cell types [29]. IRF4 deficiency facilitates the progression of BCR/ABL-induced B-ALL, while forced expression of IRF4 potently supresses the pathogenesis of BCR/ABL-induced B-ALL [28].…”