Early growth response gene (EGR1) is a transcription factor known to be a downstream effector of B cell receptor signaling and Janus kinase 1 (JAK1) signaling in diffuse large B cell lymphoma (DLBCL). While EGR1 is characterized as a tumor suppressor in leukemia and multiple myeloma, the role of EGR1 in lymphoma is unknown. Here we demonstrate that EGR1 is a potential oncogene that promotes cell proliferation in DLBCL. Immunohistochemical analysis revealed that EGR1 expression is elevated in DLBCL compared with normal lymphoid tissues and the level of EGR1 expression is higher in activated B-cell-like subtype (ABC) than germinal center B-cell-like subtype (GCB). EGR1 expression is required for the survival and proliferation of DLBCL cells. Genomic analyses demonstrated that EGR1 upregulates expression of MYC and E2F pathway genes through the CBP/p300/H3K27ac/BRD4 axis while repressing expression of the type I interferon pathway genes by interaction with the co-repressor NAB2. Genetic and pharmacological inhibition of EGR1 synergizes with the BRD4 inhibitor JQ1 or the type I interferon inducer lenalidomide in growth inhibition of ABC DLBCL both in cell cultures and xenograft mouse models. Therefore, targeting oncogenic EGR1 signaling represents a potential new targeted therapeutic strategy in DLBCL, especially for the more aggressive ABC DLBCL.

EGR1 addiction in diffuse large B cell lymphoma

Primary non-Hodgkin lymphoma of the central nervous system.

A 10-year-old, female, mixed-breed cat was presented for necropsy with history of incoordination, circling and nystagmus or fixed gaze. Grossly, slight asymmetry was observed in the right telencephalic hemisphere, mainly in the pyriform lobe. Histologically, sheets of small round neoplastic cells were observed in the pons, midbrain, thalamus and in the subcortical white matter of the parietal, occipital and pyriform lobes. Neoplastic cells were strongly labeled with anti-CD3 antibody by means of immunohistochemistry. Anti-BLA36, CD79a and MAC387 failed to label the neoplastic cells. Based on the histopathological findings and on the immunohistochemical results, a diagnosis of primary brain T-cell lymphoma was made.

/pdf/primary-brain-t-cell-lymphoma-in-a-cat-1mmxav5feh.pdf

Primary brain T-cell lymphoma in a cat.

Non-Hodgkin lymphomas (NHL) of the Central Nervous System (CNS) are rare but they nonetheless consistute a clinical, biological and therapeutic problem of great interest. Primary lymphomas of the CNS account for 2% of all malignant lymphomas and for 0.3–1.5% of all intracranial tumors. Surgery and radiotherapy afford only poor control of the disease. The most satisfactory results have been achieved with combination therapy, surgery+radiotherapy+chemiotherapy, but the optimal combination has still to be devised. Secondary neuromeningeal involvement affects a fair number of patients with systemic NHL. The symptoms are broadly the same as in CNS NHL and the treatment as problematic. There have recently been suggestions that the onset of CNS NHL may be exacerbated by immunodeficiency states such as occur in patients who have undergone organ transplantation, in autoimmune disease and, still more recently, in the acquired immunodeficiency syndrome (AIDS). The frequency of these tumors is anyway on the increase and a better insight into the disease in essential.

Non-Hodgkin lymphomas of the central nervous system.

Between 1987-1988 we treated, in a cooperative study, 13 patients in blast crisis of CGL according to Koller and Miller's regimen. We observed no return to the chronic phase of the disease, while some patients suffered major drug-induced side effects. Six patients in accelerated phase were treated with the same combination therapy. All of them responded with a return to the chronic phase for a median of 4.5 months. In our hands the combination of plicamycin and hydroxyurea was ineffective in patients with CGL in blast crisis. This regimen could deserve further evaluation in patients with CGL in acceleration.

The Plicamycin and Hydroxyurea Combination Chemotherapy for Chronic Granulocytic-leukemia in Myeloid Transformation

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Non-Hodgkin lymphomas of the central nervous system.

The Plicamycin and Hydroxyurea Combination Chemotherapy for Chronic Granulocytic-leukemia in Myeloid Transformation