Interleukin-1 Beta Gene Deregulation Associated With Chromosomal Rearrangement: A Candidate Initiating Event for Murine Radiation-Myeloid Leukemogenesis?

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Abstract
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‐1β (IL‐1β) 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‐1β is specifically deregulated in N36and 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‐1β deregulation may initiate murine leukemogenesis through the uncoupling of normal proliferative control mechanisms in multipotential hemopoietic cells.