Inactivation of the NHEJ Activity of DNA-PKcs Prevents Fanconi Anemia Pre-Leukemic HSC Expansion

Author: Srinivas CHATLA ¹ ; Andrew F WILSON ; Qishen PANG
Author Information

1. Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. Qishen.pang@cchmc.org
Publication Type:Brief Communication
Keywords: DNA damage; Fanconi anemia; Leukemic stem cells; Non-homologous end-joining
MeSH: Bone Marrow; DNA; DNA Damage; Fanconi Anemia; Hematopoietic Stem Cells; Leukemia; Stem Cells
From:International Journal of Stem Cells 2019;12(3):457-462
CountryRepublic of Korea
Language:English
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.