Childhood hematopoietic stem cells constitute the permissive window for RUNX1-ETO leukemogenesis.
Int J Hematol
; 117(6): 830-838, 2023 Jun.
Article
em En
| MEDLINE
| ID: mdl-37129801
ABSTRACT
Cancer is a very rare event at the cellular level, although it is a common disease at the body level as one third of humans die of cancer. A small subset of cells in the body harbor the cellular features that constitute a permissive window for a particular genetic change to induce cancer. The significance of a permissive window is ironically best shown by a large number of failures in generating the animal model for acute myeloid leukemia (AML) with t(8;21). Over the decades, the RUNX1-ETO fusion gene created by t(8;21) has been introduced into various types of hematopoietic cells, largely at adult stage, in mice; however, all the previous attempts failed to generate tractable AML models. In stark contrast, we recently succeeded in inducing AML with the clinical features seen in human patients by specifically introducing RUNX1-ETO in childhood hematopoietic stem cells (HSCs). This result in mice is consistent with adolescent and young adult (AYA) onset in human t(8;21) patients, and suggests that childhood HSCs constitute the permissive window for RUNX1-ETO leukemogenesis. If loss of a permissive window is induced pharmacologically, cancer cells might be selectively targeted. Such a permissive window modifier may serve as a novel therapeutic drug.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
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Subunidade alfa 2 de Fator de Ligação ao Core
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Animals
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article