Low-penetrance genetic susceptibility and resistance loci implicated in the relative risk for radiation-induced acute myeloid leukemia in mice
Inbred CBA/H mice are susceptible to radiation-induced acute myeloid leukemia (r-AML), and C57BL/6 mice are resistant. A genome-wide screen for linkage between genotype and phenotype (r-AML) of 67 affected (CBA/H × C57BL/6)F1 × CBA/H backcross mice has revealed at least 2 suggestive loci that contri...
Gespeichert in:
Veröffentlicht in: | Blood 2003-03, Vol.101 (6), p.2349-2354 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Inbred CBA/H mice are susceptible to radiation-induced acute myeloid leukemia (r-AML), and C57BL/6 mice are resistant. A genome-wide screen for linkage between genotype and phenotype (r-AML) of 67 affected (CBA/H × C57BL/6)F1 × CBA/H backcross mice has revealed at least 2 suggestive loci that contribute to the overall lifetime risk for r-AML. Neither is necessary or sufficient for r-AML, but relative risk is the net effect of susceptibility (distal chromosome 1) and resistance (chromosome 6) loci. An excess of chromosome 6 aberrations in mouse r-AML and bone marrow cells up to 6 months after irradiation in vivo suggests the locus confers a proliferative advantage during the leukemogenic process. The stem cell frequency regulator 1 (Scfr1) locus maps to distal chromosome 1 and determines the frequency of hemopoietic stem cells (HSCs) in inbred mice, suggesting that target size may be one factor in determining the relative susceptibility of inbred mice to r-AML. |
---|---|
ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2002-08-2394 |