BioProject

Leukemia stem cells (LSCs) are an attractive target in treatment of many types of blood cancers. More...

Leukemia stem cells (LSCs) are an attractive target in treatment of many types of blood cancers. There remains an incomplete understanding of the epigenetic mechanisms driving LSC formation and maintenance, and how this compares to the epigenetic regulation of normal hematopoietic stem cells (HSCs). To investigate novel mechanisms underlying the dependence of MLL-AF9 leukemia stem cells on Dnmt1, we used genome-wide expression profiling to examine changes in gene expression in Dnmt1 haploin sufficient L-GMPs as well as more differentiated leukemia cells (the bulk population of leukemia cells) compared to their control counterparts. Overall design: Bone marrow LSK (Lin- Sca-1+ c-Kit+) cells were isolated from Dnmtfl/+ Mx-Cre+ or control Dnmtfl/fl mice. These cells were transduced with MLL-AF9-IRES-GFP retrovirus for 2 days, then GFP+ cells were sorted and transplanted into C57BL/6 syngeneic sublethally irradiated (600 rad) recipients. After 2 weeks, Dnmt1 haploinsufficiency was achieved in the leukemia cells by seven injections of poly(I)poly(C). Upon development of terminal stage acute myeloid leukemia, populations of L-GMPs or bulk GFP+ leukemia cells were FACS sorted from leukemic spleens, RNA was extracted, amplified and hybridized to Affymetrix 430A 2.0 microarrays to compare changes in gene expression. There are 2 biological replicates of Dnmtfl/+ Mx-Cre+ and control L-GMPs and bulk leukemia cells. Less...