Niche-based screening identifies small-molecule inhibitors of leukemia stem cells

ABSTRACT: Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone-marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow t

ORGANISM(S): Mus musculus

SUBMITTER: Kimberly Hartwell 

PROVIDER: E-GEOD-51033 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress