Leukemic Cells Infiltrate the Ovaries Without Damaging Ovarian Reserve in an Acute Myeloid Leukemia Mouse Model.

Abstract

Leukemia is one of the most common cancers in prepubertal girls and adolescents, with advances improving survival rates. However, treatments like chemotherapy and radiation are highly gonadotoxic, often causing ovarian insufficiency, early menopause, infertility, and endocrine disorders. Fertility preservation for young female patients with cancer, especially prepubertal girls without mature germ cells, relies heavily on ovarian tissue cryopreservation. Yet, a major concern is the potential presence of leukemic cells within preserved tissue, posing a risk of reintroducing malignancy upon grafting. Additionally, the direct effects of leukemia on ovarian function remain unclear. In this study, we used an acute myeloid leukemia (AML) mouse model to explore the impact of leukemia on ovarian function. Leukemic cells infiltrated the ovaries, particularly the stromal regions and granulosa layers of antral follicles, while also being present in the spleen and liver. Despite this infiltration, ovarian structure, follicular counts, and primordial follicle reserves were largely preserved, with the notable absence of corpus luteum indicating impaired ovulation. Furthermore, leukemic infiltration induced inflammatory cytokines TNF-α and COX-2, potentially influencing ovarian health. These findings suggest opportunities for fertility preservation by selectively removing leukemic cells, though risks of malignancy remain. This model offers a platform for advancing fertility-preservation strategies during gonadotoxic cancer therapies.