Aggressive myeloid malignancies such as Acute Myeloid Leukemia (AML) and blast crisis Chronic Myeloid Leukemia are characterized by rapid and uncontrolled growth of immature cells of the myeloid lineage. Since current therapies are often ineffective in treating these diseases, there is a significant need to better understand mechanisms driving their progression, and to identify new therapeutic targets.
Myelodysplastic Syndromes (MDS) are a group of pre-leukemic disorders that arise from mutations in the hematopoietic stem cells. MDS is the most commonly diagnosed myeloid neoplasm in the United States and is associated with a 3-year survival rate of 35-45%. This significantly high mortality is in part due to a high risk of transformation to acute myelogenous leukemia (AML). There is thus a significant need to develop tractable genetic murine models of MDS initiation and progression to AML.
Concerted efforts to define the HSC bone marrow niche have pointed towards a functional role of many different cell types such as the osteoblasts, mesenchymal stromal cells, endothelial cells and the perivascular CAR cells. The significant interest in defining the microenvironment of HSCs has sparked research on defining the niche of hematological disorders that arise from these cells, such as Myelodysplastic Syndromes (MDS) and AML (Acute Myeloid Leukemia).