Interleukin-1 beta gene deregulation associated with chromosomal rearrangement: a candidate initiating event for murine radiation-myeloid leukemogenesis?
The incidence of acute myeloid leukemia (AML) in CBA/H mice following exposure to single acute doses of ionizing radiation has previously been determined. A high proportion of these AMLs are characterized by rearrangement of murine chromosome 2 in the C2 and/or E5-F regions, and there is evidence that these events are a direct consequence of radiation damage to multipotential hemopoietic cells. Using a combination of in situ chromosome hybridization and mRNA analyses, we show that the cytokine gene interleukin-1 beta (IL-1 beta) is encoded in the chromosome 2 F region and is translocated in a chromosome 2---2 rearrangement in an x-ray-induced AML (N36). Also, IL-1 beta is specifically deregulated in N36 and in two other chromosome 2-rearranged AMLs but not in a fourth, which has two cytogenetically normal chromosome 2 copies. We suggest that radiation-induced specific chromosome 2 rearrangement associated with IL-1 beta deregulation may initiate murine leukemogenesis through the uncoupling of normal proliferative control mechanisms in multipotential hemopoietic cells.
Silver
A
A
Division of Radiation Oncogenesis, Medical Research Council Radiobiology Unit, Chilton, Didcot, U.K.
Boultwood
J
J
Breckon
G
G
Masson
W
W
Adam
J
J
Shaw
A R
AR
Cox
R
R
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002874:Chromosome Mapping; D005786:Gene Expression Regulation / Q000528:radiation effects*; D015321:Gene Rearrangement; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D051379:Mice; D008808:Mice, Inbred CBA; D012150:Polymorphism, Restriction Fragment Length
D007375:Interleukin-1