The efficiency of murine MLL-ENL-driven leukemia initiation changes with age and peaks during neonatal development.

ABSTRACT: MLL rearrangements are translocation mutations that cause both acute lymphoblastic leukemia and acute myeloid leukemia (AML). These translocations can occur as sole clonal driver mutations in infant leukemias, suggesting that fetal or neonatal hematopoietic progenitors may be exquisitely sensitive to transformation by MLL fusion proteins. To test this possibility, we used transgenic mice to induce one translocation product, MLL-ENL, during fetal, neonatal, juvenile and adult stages of life. When MLL-ENL was induced in fetal or neonatal mice, almost all died of AML. In contrast, when MLL-ENL was induced in adult mice, most survived for >1 year despite sustained transgene expression. AML initiation was most efficient when MLL-ENL was induced in neonates, and even

SUBMITTER: Okeyo-Owuor T 

PROVIDER: S-EPMC6693010 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature