TEL (ETV6)-AML1 (RUNX1) initiates self-renewing fetal pro-B cells in association with a transcriptional program shared with embryonic stem cells in mice.
Stem Cells
; 31(2): 236-47, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23135987
ABSTRACT
The initial steps involved in the pathogenesis of acute leukemia are poorly understood. The TEL-AML1 fusion gene usually arises before birth, producing a persistent and covert preleukemic clone that may convert to precursor B cell leukemia following the accumulation of secondary genetic "hits." Here, we show that TEL-AML1 can induce persistent self-renewing pro-B cells in mice. TEL-AML1+ cells nevertheless differentiate terminally in the long term, providing a "window" period that may allow secondary genetic hits to accumulate and lead to leukemia. TEL-AML1-mediated self-renewal is associated with a transcriptional program shared with embryonic stem cells (ESCs), within which Mybl2, Tgif2, Pim2, and Hmgb3 are critical and sufficient components to establish self-renewing pro-B cells. We further show that TEL-AML1 increases the number of leukemia-initiating cells that are generated in collaboration with additional genetic hits, thus providing an overall basis for the development of novel therapeutic and preventive measures targeting the TEL-AML1-associated transcriptional program.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
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Leucemia-Linfoma Linfoblástico de Células Precursoras B
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Regulación Neoplásica de la Expresión Génica
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Proteínas de Fusión Oncogénica
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Subunidad alfa 2 del Factor de Unión al Sitio Principal
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Células Madre Embrionarias
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Células Precursoras de Linfocitos B
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Stem Cells
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón