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Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin.
Leukemia ; 31(5): 1079-1086, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27807368
ABSTRACT
The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Proteínas Nucleares / Leucemia / Proteínas de Ligação a DNA / Doenças Fetais Aspecto clínico: Diagnóstico / Etiologia Limite: Animais / Feminino / Humanos / Gravidez Idioma: Inglês Revista: Leukemia Assunto da revista: Hematologia / Neoplasias Ano de publicação: 2017 Tipo de documento: Artigo País de afiliação: China