Senescence in the bone marrow microenvironment: A driver in development of therapy-related myeloid neoplasms

•Cytotoxic therapy increases the risk for therapy-related myeloid neoplasms (t-MN).•While HSC-intrinsic effects are crucial, t-MN is also dependent on extrinsic factors.•Cytotoxic therapy drives senescence in the bone marrow microenvironment (BMME).•Current studies support a role for BMME senescence in the development of t-MN.•Targeting of senescent BMSCs may alleviate BM dysfunction and mitigate t-MN. Therapy-related myeloid neoplasms (t-MN) are a growing concern due to the continued use of cytotoxic therapies to treat malignancies. Cytotoxic therapies have been shown to drive therapy-induced senescence in normal tissues, including in the bone marrow microenvironment (BMME), which plays a crucial role in supporting normal hematopoiesis. This review examines recent work that focuses on the contribution of BMME senescence to t-MN pathogenesis, as well as offers a perspective on potential opportunities for therapeutic intervention.