Soil and Seed: Coconspirators in Therapy-Induced Myeloid Neoplasms

In this issue of Blood Cancer Discovery, Stoddart and colleagues describe cooperative effects of exposing both the bone marrow microenvironment of recipient mice and donor hematopoietic stem and progenitor cells (HSPC) to an alkylating agent in a genetically accurate model of therapy-induced myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) characterized by chromosome 5q deletions. The authors further implicate senescence of alkylator-treated mesenchymal stem cells (MSC) as contributing to the microenvironmental damage and subsequent therapy-induced myeloid neoplasms (tMN). Loss of Trp53 function and somatic mutations in other DNA damage response (DDR) genes were associated with overt AML in this model. Together, these studies shed new light on the complex pathogenesis of tMN and establish a robust model for biologic and preclinical investigation.