In recent years, there is growing interest regarding the roles of senescent bone marrow (BM) microenvironment in the initiation of leukemia. Aged mice transplanted with AML1-ETO (AML1-ETO fusion protein)-positive hematopoietic stem cells (HSCs) present with a significant increase in the frequency of AML-ETO-positive early progenitor cells in BM as well as an increase of immature myeloid cells compared to young recipients (Vas et al., 2012). BM mesenchymal stem cells (MSCs) from myelodysplastic syndromes (MDS) animal models and MDS patients exhibit impaired proliferation and differentiation potentials, abnormal cytokine secretion, and dysregulated gene expression profile (Lopez-Villar et al., 2009; Geyh et al., 2013; Mattiucci et al., 2018). However, the causal relationship between senescent BM microenvironment and leukemia development is unclear. Whether senescent BM microenvironment initiates or accelerates leukemia development remains unknown.