Inactivation of the NHEJ Activity of DNA-PKcs Prevents Fanconi Anemia Pre-Leukemic HSC Expansion
International Journal of Stem Cells
;
: 457-462, 2019.
Article
in English
| WPRIM
| ID: wpr-785828
ABSTRACT
Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure and high risk of cancer particularly leukemia. Here we show that inactivation of the non-homologous end-joining (NHEJ) activity of DNA-PKcs prevented DNA damage-induced expansion of FA pre-leukemic hematopoietic stem cells (HSCs). Furthermore, we performed serial BM transplantation to demonstrate that the DNA damage-induced expanded FA HSC compartment contained pre-leukemic stem cells that required the NHEJ activity of DNA-PKcs to induce leukemia in the secondary recipients. These results suggest that NHEJ may collaborate with FA deficiency to promote DNA damage-induced expansion of pre-leukemic HSCs.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Stem Cells
/
Bone Marrow
/
DNA Damage
/
DNA
/
Hematopoietic Stem Cells
/
Leukemia
/
Fanconi Anemia
Language:
English
Journal:
International Journal of Stem Cells
Year:
2019
Type:
Article
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