Functional Equivalence of Gamma- and X-Ray Irradiation for Long-Term Hematopoietic and AML Transplant Outcomes in Mice

Total-body irradiation (TBI) is routinely used for myeloablation prior to mouse hematopoietic cell transplant. Widespread transition from ¹³⁷ Cs <i>γ</i> -irradiators to X-ray systems has raised questions about whether these modalities yield equivalent biological outcomes. Although prior studies compared <i>γ</i> and X-ray irradiation in healthy syngeneic transplants, their performance in reciprocal congenic models and in primary acute myeloid leukemia (AML) transplant remains unclear. Here, we systematically evaluated <i>γ</i> and X-ray irradiation across dose and dose-rate conditions, and tested dose equivalents in CD45.1/CD45.2 reciprocal transplants and in AML transplant models. While each modality exhibited distinct early effects, both ultimately supported comparable long-term donor chimerism in congenic transplants and equivalent AML engraftment, leukemic burden, and disease progression. These findings indicate that, with proper dose calibration, X-ray irradiation is a functionally effective alternative to <i>γ</i> -irradiation for normal and malignant transplant studies.