Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements.
Cell Rep
; 37(4): 109900, 2021 10 26.
Article
em En
| MEDLINE
| ID: mdl-34706236
ABSTRACT
Infant MLL-AF4-driven acute lymphoblastic leukemia (ALL) is a devastating disease with dismal prognosis. A lack of understanding of the unique biology of this disease, particularly its prenatal origin, has hindered improvement of survival. We perform multiple RNA sequencing experiments on fetal, neonatal, and adult hematopoietic stem and progenitor cells from human and mouse. This allows definition of a conserved fetal transcriptional signature characterized by a prominent proliferative and oncogenic nature that persists in infant ALL blasts. From this signature, we identify a number of genes in functional validation studies that are critical for survival of MLL-AF4+ ALL cells. Of particular interest are PLK1 because of the readily available inhibitor and ELOVL1, which highlights altered fatty acid metabolism as a feature of infant ALL. We identify which aspects of the disease are residues of its fetal origin and potential disease vulnerabilities.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Ácidos Graxos
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Feto
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Newborn
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article