DNA damage response and preleukemic fusion genes induced by ionizing radiation in umbilical cord blood hematopoietic stem cells.
Antigens, CD34
/ metabolism
Apoptosis
/ radiation effects
DNA Breaks, Double-Stranded
/ radiation effects
DNA Repair
/ genetics
Fetal Blood
/ radiation effects
Fusion Proteins, bcr-abl
/ genetics
Gene Fusion
/ genetics
Hematopoietic Stem Cells
/ radiation effects
Histones
/ genetics
Humans
Infant, Newborn
Leukemia
/ genetics
Lymphocytes
/ radiation effects
Preleukemia
/ genetics
Radiation, Ionizing
Tumor Suppressor p53-Binding Protein 1
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 08 2020
24 08 2020
Historique:
received:
25
11
2019
accepted:
27
07
2020
entrez:
26
8
2020
pubmed:
26
8
2020
medline:
8
1
2021
Statut:
epublish
Résumé
There is clear evidence that ionizing radiation (IR) causes leukemia. For many types of leukemia, the preleukemic fusion genes (PFG), as consequences of DNA damage and chromosomal translocations, occur in hematopoietic stem and progenitor cells (HSPC) in utero and could be detected in umbilical cord blood (UCB) of newborns. However, relatively limited information is available about radiation-induced apoptosis, DNA damage and PFG formation in human HSPC. In this study we revealed that CD34+ HSPC compared to lymphocytes: (i) are extremely radio-resistant showing delayed time kinetics of apoptosis, (ii) accumulate lower level of endogenous DNA damage/early apoptotic γH2AX pan-stained cells, (iii) have higher level of radiation-induced 53BP1 and γH2AX/53BP1 co-localized DNA double stranded breaks, and (iv) after low dose of IR may form very low level of BCR-ABL PFG. Within CD34+ HSPC we identified CD34+CD38+ progenitor cells as a highly apoptosis-resistant population, while CD34+CD38- hematopoietic stem/multipotent progenitor cells (HSC/MPP) as a population very sensitive to radiation-induced apoptosis. Our study provides critical insights into how human HSPC respond to IR in the context of DNA damage, apoptosis and PFG.
Identifiants
pubmed: 32839487
doi: 10.1038/s41598-020-70657-z
pii: 10.1038/s41598-020-70657-z
pmc: PMC7445283
doi:
Substances chimiques
Antigens, CD34
0
H2AX protein, human
0
Histones
0
TP53BP1 protein, human
0
Tumor Suppressor p53-Binding Protein 1
0
Fusion Proteins, bcr-abl
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13722Références
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