MUM1/IRF4: a review
ABSTRACT MUM1/IRF4 protein is a member of the interferon regulatory factor (IRF) family of transcriptional factors initially described as downstream regulators of interferon signaling. The quantity of this factor varies within the hematopoietic system in a lineage and stage-specific way. It is considered to be a key regulator of several steps in lymphoid, myeloid, and dendritic cell differentiation and maturation. MUM1/IRF4 expression is observed in many lymphoid and myeloid malignancies, and may be a promising target for the treatment of some of these neoplasms. We reviewed the literature on MUM1/IRF4, with emphasis on the pathologic aspects of this marker in reactive and malignant hematologic and nonhematologic conditions.
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ABSTRACT: Interferon regulatory factor 4 (IRF4) expression is detected in many lymphoid and myeloid malignancies, and may be a promising therapeutic target. IRF4 is strongly expressed in classical Hodgkin lymphoma (cHL) and its expression is up-regulated by CD40L and down-regulated by both anti-proliferative and pro-apoptotic stimuli. This study analysed the effects of IRF4 silencing in a panel of HL-derived cell lines. We demonstrated that IRF4 down-modulation determined a remarkable decrease of both cell number and clonogenic growth in L-1236, L-428, KM-H2 and HDLM-2 cells, but not in IRF4-negative L-540 cells. IRF4 silencing induced apoptosis, as evaluated by caspase-3 activation and Annexin-V staining and up-regulation of the pro-apoptotic molecule Bax. CD40 engagement by both soluble and membrane bound-CD40L almost totally reduced IRF4 down-modulation and growth inhibition by IRF4 silencing in both L-1236 and L-428 cells. Finally, IRF4 silencing decreased CCL5 secretion in all HL cell lines tested and CCL17 in KM-H2 cells. Taken together, our results demonstrated that IRF4 down-modulation by IRF4 silencing was reversed by CD40 engagement, inhibited HL cells proliferation, induced apoptosis and decreased CCL5 secretion, thus suggesting that IRF4 may be involved in HL pathobiology.British Journal of Haematology 01/2011; 152(2):182-90. DOI:10.1111/j.1365-2141.2010.08497.x · 4.96 Impact Factor
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ABSTRACT: This review article offers some useful panels of immunohistochemical stains and discusses their use in determining a hematopathology diagnosis. As a comprehensive review of the vast array of hematolymphoid malignancies is beyond the scope of this study, the suggestions are based on broad morphologic categories such as follicular proliferations, paracortical expansions, diffuse small-cell infiltrates, diffuse large-cell infiltrates, and Hodgkin-like infiltrates. The review article also discusses the most common hematolymphoid malignancies and their immunohistochemical profiles, and how to use immunophenotyping to differentiate them from other entities. Common diagnostic pitfalls and misconceptions about certain antibodies will also be discussed. New antibodies, such as SOX11, will also be explored in the context of specific disease entities for which they may be of use.Advances in anatomic pathology 03/2011; 18(2):133-51. DOI:10.1097/PAP.0b013e3182026dbd · 3.10 Impact Factor
Chapter: Bone Marrow[Show abstract] [Hide abstract]
ABSTRACT: This chapter provides an overview of immunohistochemical markers used frequently in assessing bone marrow diseases. These disease entities include lymphoid and myeloid leukemias, both acute and chronic, lymphoproliferative disorders, T and B cell neoplasms/lymphomas, myeloproliferative neoplasms, myelodysplastic syndromes, mast cell disease, plasma cell dyscrasias, and metastatic tumors to the bone marrow.There is quite a bit of overlap between the markers used in the bone marrow workup for lymphoid diseases and lymphoma (Chap. 27), thus a review of that chapter might be helpful in the workup of lymphoproliferative disorders. Also the marrow can be the site for metastatic tumors. The workup of metastatic disease to the marrow is the same as in any other site (Chap. 7) with the exception of markers that are rendered useless by the decalcification process. KeywordsBone marrow-T and B cells-Blast-Acute lymphoblastic leukemia-Acute myelogenous leukemia-Myeloproliferative neoplasms-Myelodysplastic syndromes-Lymphoma-ChronicHandbook of Practical Immunohistochemistry, 06/2011: pages 493-500;