Registro completo |
Provedor de dados: |
BJMBR
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País: |
Brazil
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Título: |
CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice
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Autores: |
Lange,A.P.
Almeida,L.Y.
Araújo Silva,C.L.
Scheucher,P.S.
Chahud,F.
Krause,A.
Bohlander,S.K.
Rego,E.M.
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Data: |
2019-01-01
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Ano: |
2019
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Palavras-chave: |
Leukemia
CEBPA
CALM/AF10
Transgenic mice
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Resumo: |
Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.
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Tipo: |
Info:eu-repo/semantics/article
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Idioma: |
Inglês
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Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000600604
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Editor: |
Associação Brasileira de Divulgação Científica
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Relação: |
10.1590/1414-431x20198424
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Formato: |
text/html
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Fonte: |
Brazilian Journal of Medical and Biological Research v.52 n.6 2019
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Direitos: |
info:eu-repo/semantics/openAccess
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