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Publication : Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements.

First Author  Symeonidou V Year  2021
Journal  Cell Rep Volume  37
Issue  4 Pages  109900
PubMed ID  34706236 Mgi Jnum  J:337687
Mgi Id  MGI:6883822 Doi  10.1016/j.celrep.2021.109900
Citation  Symeonidou V, et al. (2021) Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements. Cell Rep 37(4):109900
abstractText  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.
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