Histone acetyl-transferase Kat2a preserves leukemia stem cells through frequent transcriptional firing of metabolic and regulatory gene promoters and maintenance of a largely invariant self-renewal program.
Convergent transcription and stalling of transcription are enriched at DNA breakpoints found in acute lymphoblastic leukemia and associate with DNA structures and sequences that mediate genetic instability.
A comprehensive analysis of long noncoding RNAs in the hematopoietic system reveals their dynamic regulation and a loss-of-function screen identifies some required for leukemia progression and involved in normal myeloid differentiation.
Anti-targets are proteins that cause problems when inhibited along with an intended target and our novel chemical strategy affords unprecedented selectivity in the context of FLT3 vs. KIT inhibition for treatment of a devastating blood cancer.
The identification of key determinants of LSC “stemness” and LSC differentiation that is reversible through an epigenetic mechanism may have considerable implications in understanding leukemia and designing effective therapies.