title: GFI1B, EVI5, MYB--additional genes that cooperate with the human BCL6 gene to promote the development of lymphomas.
abstract: The BCL6 gene, which is expressed in certain B- and T-cell human lymphomas, is involved with chromosomal rearrangements and mutations in a number of these neoplasms. Lymphomagenesis is believed to evolve through a multi-step accumulation of genetic alterations in these tumors. We used retroviral insertional mutagenesis in transgenic mice expressing the human BCL6 transgene in order to identify genes that cooperate with BCL6 during lymphomatous transformation. We previously reported PIM1 as the most frequently recurring cooperating gene in this model. We now report three newly identified cooperating genes-GFI1B, EVI5, and MYB-that we identified in the lymphomas of retroviral-injected BCL6 transgenic mice (but not in retroviral-injected non-transgenic controls); mRNA and protein expression of GFI1B and EVI5 were decreased in the murine tumors, whereas MYB mRNA and protein expression were increased or decreased. These findings correlated with protein expression in human lymphomas, both B- and T-cell. Improved therapy of lymphomas may necessitate the development of combinations of drugs that target the alterations specific to each neoplasm.
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: beverly.baron@uchospitals.edu.
authors.forename: Beverly W
authors.initials: BW
authors.lastname: Baron
authors.forename: John
authors.initials: J
authors.lastname: Anastasi
authors.forename: Juraj
authors.initials: J
authors.lastname: Bies
authors.forename: Poluru L
authors.initials: PL
authors.lastname: Reddy
authors.forename: Loren
authors.initials: L
authors.lastname: Joseph
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thirman
authors.forename: Kristen
authors.initials: K
authors.lastname: Wroblewski
authors.forename: Linda
authors.initials: L
authors.lastname: Wolff
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Baron
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020690:GTPase-Activating Proteins; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020626:Oncogene Proteins v-myb / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C084103:BCL6 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C105043:Evi5 protein, mouse; D020690:GTPase-Activating Proteins; C486395:Gfi1b protein, mouse; D020626:Oncogene Proteins v-myb; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors
keywords: BCL6 transgenic mice; Cooperating genes; EVI5; GFI1B; Lymphoma development; MYB
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