Expression Of The Fetal Hematopoiesis Regulator FEV Indicates Leukemias Of Prenatal Origin

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 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 FEV was expressed in most infant leukemia samples,but not in adult samples,in accord with the known pre-natal origins of the former.We further determined the majority of pediatric acute lymphoid and myeloid leukemias(ALL and AML)were FEV-positive.Moreover FEV-knockdown markedly impaired the leukemiapropagating 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.