The hematopoietic microenvironment while crucial for maintaining healthy self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) may also be a source for deleterious signals that may cause damage to HSPCs leading to disease (1,2). Previous studies have shown that alterations to niche components can trigger or aid in disease progression. A study to generate an improved xenograft mouse model of myelodysplasia syndrome (MDS) found that co-transplantation of patient stem cells with stromal cells increased disease engraftment, suggesting that the stromal cells are important in disease initiation and maintenance (3). Acute myeloid leukemia (AML) was triggered in mice by activation of β-catenin in osteoblast which lead to overexpression of the Notch ligand Jagged1 and upregulation of the Notch receptor in HSPCs (4).