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CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice
Lange, A P; Almeida, L Y; Araújo Silva, C L; Scheucher, P S; Chahud, F; Krause, A; Bohlander, S K; Rego, E M.
  • Lange, A P; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Divisão de Hematologia. Ribeirão Preto. BR
  • Almeida, L Y; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Divisão de Hematologia. Ribeirão Preto. BR
  • Araújo Silva, C L; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Divisão de Hematologia. Ribeirão Preto. BR
  • Scheucher, P S; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Divisão de Hematologia. Ribeirão Preto. BR
  • Chahud, F; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Patologia e Medicina Legal. Ribeirão Preto. BR
  • Krause, A; Universidade Federal de Santa Maria. Laboratório de Análises Clínicas Veterinárias. Santa Maria. BR
  • Bohlander, S K; University of Auckland. Department of Molecular Medicine and Pathology. NZ
  • Rego, E M; Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Divisão de Hematologia. Ribeirão Preto. BR
Braz. j. med. biol. res ; 52(6): e8424, 2019. tab, graf
Article in English | LILACS | ID: biblio-1001535
ABSTRACT
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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Full text: Available Index: LILACS (Americas) Main subject: Leukemia, Myeloid, Acute / CCAAT-Enhancer-Binding Protein-alpha / Haploinsufficiency / Hematopoiesis Type of study: Prognostic study Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2019 Type: Article Affiliation country: Brazil / New Zealand Institution/Affiliation country: Universidade Federal de Santa Maria/BR / Universidade de São Paulo/BR / University of Auckland/NZ

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Full text: Available Index: LILACS (Americas) Main subject: Leukemia, Myeloid, Acute / CCAAT-Enhancer-Binding Protein-alpha / Haploinsufficiency / Hematopoiesis Type of study: Prognostic study Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2019 Type: Article Affiliation country: Brazil / New Zealand Institution/Affiliation country: Universidade Federal de Santa Maria/BR / Universidade de São Paulo/BR / University of Auckland/NZ