Absence of the Shb gene in mixed-lineage leukemia MLL-AF9 cells increases latency in mice despite higher proliferation rates in vitro.
Exp Cell Res
; 397(2): 112368, 2020 12 15.
Article
en En
| MEDLINE
| ID: mdl-33220260
Mixed lineage leukemia (MLL) arises from several KMT2A-gene chromosomal translocations. Shb gene deficiency has been found to exhibit pleiotropic effects in different models of leukemia, and consequently, this study aimed to investigate MLL-AF9-induced leukemia in Shb deficiency. Bone marrow cells from wild type and Shb knockout (KO) mice were transduced with the MLL-AF9 gene. Shb KO MLL-AF9 cells proliferated at an increased rate, exhibited altered expression of certain cytokine genes (Kitl, Csf3, IL6, IL1b) and higher expression of cell cycle genes (Ccnd2, Ccne1). Mice receiving Shb KO MLL-AF9 cells showed longer latency without displaying any difference in rates of leukemic cell proliferation, indicating a dichotomy between the in vitro and in vivo phenotypes. The mice with Shb deficient MLL-AF9 cells had a lower content of leukemic bone marrow cells allowing elevated normal hematopoiesis, explaining the longer latency. Finally, Shb knockout GFP-positive bone marrow cells showed a higher percentage of cells expressing myeloid markers. The result suggests a role of Shb in the progression of leukemia and that the relevance of the Shb gene is context-dependent as inferred from the differences between the in vivo and in vitro responses. These findings help to obtain an increased understanding of human MLL-AF9 leukemia.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia Experimental
/
Regulación Leucémica de la Expresión Génica
/
Proteínas de Fusión Oncogénica
/
Transformación Celular Neoplásica
/
Proteínas Proto-Oncogénicas
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Proliferación Celular
/
Proteína de la Leucemia Mieloide-Linfoide
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2020
Tipo del documento:
Article
País de afiliación:
Suecia
Pais de publicación:
Estados Unidos