SIRT1 regulates enhanced mitochondrial respiration and leukemogenicity in CML stem cells

Chronic myeloid leukemia (CML) results from hematopoietic stem cell transformation by the BCR-ABL tyrosine kinase. We have shown that the SIRT1 deacetylase is overexpressed in CML LSC, and may contribute to their maintenance. Here, using genetic deletion of SIRT1 in transgenic CML mice, we definitively demonstrate that SIRT1 is required for leukemia development, and reveal its critical role in mediating increased mitochondrial respiration in CML LSC. Overall design: Bone marrow LSK cells were sorted from SIRT1 deleted (cre+) and control (cre-) CML mice and resuspended into RLT buffer and RNA is extracted. Four biological replicates were used from each genetic group. RNA samples were quality checked and proceeded to library preparation.