Fetal context conveys heritable protection against MLL-rearranged AML that depends on MLL3.

ABSTRACT:

Abstract

MLL rearrangements (MLLrs) are the most common cause of congenital and infant leukemias. MLLrs arise prior to birth and can transform fetal/neonatal progenitors with the help of only a few additional cooperating mutations. Despite the low threshold for transformation, infant leukemias are rare, and congenital leukemias, which arise before birth, are even less common. These observations raise the question of whether mechanisms exist to suppress leukemic transformation during fetal life, thereby protecting the developing fetus from malignancy during a period of rapid hematopoietic progenitor expansion. To test this possibility, we used a mouse model of temporally controlled MLL::ENL expression to show that fetal MLL::ENL exposure establishes a heritable, leukemia-resistant s

SUBMITTER: Mendoza-Castrejon J 

PROVIDER: S-EPMC12758594 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature