In this issue of Blood, Feng et al(1) describe a novel mouse model by which deletion of a single copy of the 9p21 tumor suppressor locus induces an aberrant bone marrow (BM) microenvironment, leading to loss of support for hematopoiesis, increased marrow fibrosis, and development of a fatal myelodysplastic/myeloproliferative (MDS/MPN) disorder.