Cellular kinetics of hematopoietic cells with Sfpi1 deletion are present at different frequencies in bone-marrow and spleen in X-irradiated mice.

PURPOSE: Acute myeloid leukemia (AML) is a major cancer in the human population exposed to ionizing radiation. Several past studies using a mouse model of radiation-induced AML (rAML) have shown that hemizygous deletion of the Sfpi1 gene ( HDSG ) is an initiating event for development of rAML. Although HDSG can occur in hematopoietic stem cells (HSCs) soon after radiation exposure, the cellular kinetics of HSCs carrying HDSG in various hematopoietic tissues after X-irradiation is unclear. In this study, we examined the difference in frequency of HDSG in HSC-Rich hematopoietic Cell population (HRCs) from bone marrow and spleen of C3H mice irradiated with 3 Gy X-rays.

MATERIALS AND METHODS: We examined the time course of the change in Sfpi1 gene deletion in HRCs following X-ray irradiation (IR). 8-weeks old male C3H mice were irradiated 3 Gy of whole-body X-ray (1Gy/min) and mice were sacrificed at 1, 4, 8, and 26 weeks after IR. Then, HSPCs were isolated from bone marrow (BM) of femur and spleen, the frequency of HSPCs with Sfpi1 gene deletion was analyzed by FISH.

RESULTS AND CONCLUSIONS: The frequency of HRCs with HDSG in both bone marrow and spleen was increased 1 week after X-irradiation. Then, the frequency of HRCs with HDSG in bone marrow showed a gradual decrease from 4 to 26 weeks, whereas HRCs with HDSG in spleen remained high, even at 26 weeks after X-irradiation. The different responses may reflect differences in hematopoietic cell dynamics in bone marrow and spleen. HDSG is less likely to be eliminated, particularly in the spleen, after X-irradiation. The spleen as well as bone marrow of the femur may be major sites of rAML development.