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Mapping of MN1 sequences necessary for myeloid transformation.
Kandilci, Ayten; Surtel, Jacqueline; Janke, Laura; Neale, Geoffrey; Terranova, Sabrina; Grosveld, Gerard C.
Afiliação
  • Kandilci A; Department of Genetics, St Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
PLoS One ; 8(4): e61706, 2013.
Article em En | MEDLINE | ID: mdl-23626719
ABSTRACT
The MN1 oncogene is deregulated in human acute myeloid leukemia and its overexpression induces proliferation and represses myeloid differentiation of primitive human and mouse hematopoietic cells, leading to myeloid leukemia in mouse models. To delineate the sequences within MN1 necessary for MN1-induced leukemia, we tested the transforming capacity of in-frame deletion mutants, using retroviral transduction of mouse bone marrow. We found that integrity of the regions between amino acids 12 to 458 and 1119 to 1273 are required for MN1's in vivo transforming activity, generating myeloid leukemia with some mutants also producing T-cell lympho-leukemia and megakaryocytic leukemia. Although both full length MN1 and a mutant that lacks the residues between 12-228 (Δ12-228 mutant) repressed myeloid differentiation and increased myeloproliferative activity in vitro, the mutant lost its transforming activity in vivo. Both MN1 and Δ12-228 increased the frequency of common myeloid progentiors (CMP) in vitro and microarray comparisons of purified MN1-CMP and Δ12-228-CMP cells showed many differentially expressed genes including Hoxa9, Meis1, Myb, Runx2, Cebpa, Cebpb and Cebpd. This collection of immediate MN1-responsive candidate genes distinguishes the leukemic activity from the in vitro myeloproliferative capacity of this oncoprotein.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Regulação Neoplásica da Expressão Gênica / Transformação Celular Neoplásica / Sequência de Aminoácidos / Deleção de Sequência / Proteínas Oncogênicas / Células Mieloides / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Mieloide Aguda / Regulação Neoplásica da Expressão Gênica / Transformação Celular Neoplásica / Sequência de Aminoácidos / Deleção de Sequência / Proteínas Oncogênicas / Células Mieloides / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos