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oai:repisalud.isciii.es:20.500.12105/261302025-12-18T12:56:23Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Sanchez, Agustin author Setién, F author Martinez, Natalia author Oliva-Martinez, Jose Luis author Herranz, M author Fraga, M-F author Alaminos, M author Esteller, M author Rojas-Cabañeros, Jose Maria author 2008-08-21 Spry2 has been characterized as a negative regulator of the extracellular-regulated kinase (ERK) pathway. In this study we analysed whether epigenetic alterations of hSpry2 promoter occur in human lymphoid/hematopoietic malignancies. Our results revealed that hSpry2 promoter was hypermethylated in the HT cell line derived from a B-cell diffuse lymphoma, which correlated with decreased hSpry2 expression. We detected deregulation of the ERK pathway in these cells, but not in other blood cell lines expressing hSpry2. In addition, the ectopic overexpression of hSpry2 in HT cells drastically reduced the activation of ERK upon phorbol 12-myristate-13-acetate stimulation. Nude mice inoculated with HT mock cells developed tumors seven times larger than those from HT-hSpry2-transfected cells. We found hypermethylation of hSpry2 promoter in 37% (26 cases out of 71) of primary tumors from patients with B-cell diffuse lymphoma but none in normal B lymphocytes from 37 healthy individuals. Finally, we detected that hSpry2 promoter hypermethylation was associated with a significant decrease in the 5-year survival rate. These data suggest that hSpry2 could be important in lymphoid malignancies. Sánchez A, Setién F, Martinez N, Oliva JL, Herranz M, Fraga MF, Alaminos M, Esteller M, Rojas JM. Epigenetic inactivation of the ERK inhibitor Spry2 in B-cell diffuse lymphomas. Oncogene. 2008 Aug 21;27(36):4969-72. 10.1038/onc.2008.129 1476-5594 0950-9232 Oncogene 18427547 https://hdl.handle.net/20.500.12105/26130 hSpry2 Epigenetic Lymphomas B cells Suppressor gene Epigenetic inactivation of the ERK inhibitor Spry2 in B-cell diffuse lymphomas