Alteration and abnormal expression of the c-myc oncogene in human multiple myeloma.
ABSTRACT Structural alterations of the c-myc oncogene in human Burkitt's lymphoma and mouse plasmacytoma suggest that this oncogene is involved in several B cell neoplasms. The possibility of c-myc alterations in human myeloma has not been explored, probably because the low proliferative activity characteristic of this tumor impairs the propagation of representative cell lines for the performance of adequate cytogenetic studies. This report describes alterations in the c-myc locus with concomitant elevated expression of mRNA in the tumor cells of two of 37 patients with multiple myeloma. In one case, somatic cell hybrid studies revealed that the cloned rearranged DNA was entirely derived from chromosome 8, thus indicating a novel mechanism of c-myc activation different from that in Burkitt's lymphoma. Seven other patients exhibited five- to 12-fold overexpression of c-myc RNA when compared with normal marrow cells. Elevated mRNA expression in about one fourth of our patients suggests that the c-myc oncogene has a pathogenetic role in the evolution of multiple myeloma.
Full-textDOI: · Available from: Franco Narni, May 29, 2015
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ABSTRACT: OBJECTIVES: To report a patient with primary effusion lymphoma who was negative for human herpesvirus-8 (HHV-8), human immunodeficiency virus, Epstein-Barr virus, hepatitis C virus, and hepatitis B virus, as well as review 54 reported cases of HHV-8-unrelated primary effusion lymphoma (PEL)-like lymphoma in the literature to clarify the nature of this entity. METHODS: The patients' characteristics, clinical presentation, pathogenesis, morphologic-immunophenotypic features, clinical management, and prognosis were studied. RESULTS: HHV-8-negative PEL-like lymphomas often occur in immunocompetent and elderly patients, are sometimes associated with chronic inflammation-related fluid overload, are mostly large B-cell or large B-cell with plasmacytic differentiation type, and are associated with a better prognosis. CONCLUSIONS: In various aspects, HHV-8-unrelated PEL-like lymphoma is a different entity from HHV-8-related PEL. Immunophenotype, morphology, and c-myc/8q24 status should be included for differential diagnosis. A test for c-myc or 8q24 abnormalities should be recommended for subdividing HHV-8-unrelated PEL-like lymphoma, which may have benefits in patient management.American Journal of Clinical Pathology 07/2013; 140(2-2):258-73. DOI:10.1309/AJCPHZ3CHO4HUWET · 3.01 Impact Factor
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ABSTRACT: High level MYC expression is associated with almost all human cancers. JQ1, a chemical compound that inhibits MYC expression is therapeutically effective in preclinical animal models in midline carcinoma, and Burkitt's lymphoma (BL). Here we show that JQ1 does not inhibit MYC expression to a similar extent in all tumor cells. The BL cells showed a ∼90% decrease in MYC transcription upon treatment with JQ1, however, no corresponding reduction was seen in several non-BL cells. Molecularly, these differences appear due to requirements of Brd4, the most active version of the Positive Transcription Elongation Factor B (P-TEFb) within the Super Elongation Complex (SEC), and transcription factors such as Gdown1, and MED26 and also other unknown cell specific factors. Our study demonstrates that the regulation of high levels of MYC expression in different cancer cells is driven by unique regulatory mechanisms and that such exclusive regulatory signatures in each cancer cells could be employed for targeted therapeutics.PLoS ONE 01/2014; 9(1):e87003. DOI:10.1371/journal.pone.0087003 · 3.53 Impact Factor
10/2010; 1. DOI:10.1016/S2210-7789(10)60071-2