CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice
Braz. j. med. biol. res
;
52(6): e8424, 2019. tab, graf
Article
Dans Anglais
| 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.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Leucémie aigüe myéloïde
/
Protéine alpha liant les séquences stimulatrices de type CCAAT
/
Haploinsuffisance
/
Hématopoïèse
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
langue:
Anglais
Texte intégral:
Braz. j. med. biol. res
Thème du journal:
Biologie
/
Médicament
Année:
2019
Type:
Article
Pays d'affiliation:
Brésil
/
Nouvelle-Zélande
Institution/Pays d'affiliation:
Universidade Federal de Santa Maria/BR
/
Universidade de São Paulo/BR
/
University of Auckland/NZ
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