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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.
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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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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