西亚试剂：Unique and Independent Roles for MLL in Adult Hematopoietic

发布时间：2025-09-26

Unique and Independent Roles for MLL in Adult Hematopoietic Stem Cells and Progenitors

Craig D. Jude,1 Leslie Climer,1 Diyong Xu,1 Erika Artinger,1 Jill K. Fisher,2,3 and Patricia Ernst1,

1 Department of Genetics and Norris Cotton Cancer Center, Dartmouth Medical School, 725 Remsen, HB7400, Hanover, NH 03755, USA
2 Howard Hughes Medical Institute, Boston, MA 02115, USA
3 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA

Corresponding author
Patricia Ernst

The Mixed Lineage Leukemia (MLL) gene is essential for embryonic hematopoietic stem cell (HSC) development, but its role during adult hematopoiesis is unknown. Using an inducible knockout model, we demonstrate that Mll is essential for the maintenance of adult HSCs and progenitors, with fatal bone marrow failure occurring within 3 weeks of Mll deletion. Mll-deficient cells are selectively lost from mixed bone marrow chimeras, demonstrating their failure to self-renew even in an intact bone marrow environment. Surprisingly, HSCs lacking Mll exhibit ectopic cell-cycle entry, resulting in the depletion of quiescent HSCs. In contrast, Mll deletion in myelo-erythroid progenitors results in reduced proliferation and reduced response to cytokine-induced cell-cycle entry. Committed lymphoid and myeloid cells no longer require Mll, defining the early multipotent stages of hematopoiesis as Mll dependent. These studies demonstrate that Mll plays selective and independent roles within the hematopoietic system, maintaining quiescence in HSCs and promoting proliferation in progenitors.