A5053085600- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Histone Deacetylase Inhibitors Research
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- Hematopoietic Stem Cell Transplantation
Memorial Sloan Kettering Cancer Center
2022-2025
Cancer stem cells are essential for initiation and therapy resistance of many cancers, including acute myeloid leukemias (AML). Here, we apply functional genomic profiling to diverse human leukemias, high-risk MLL- NUP98-rearranged specimens, using label tracing in vivo. Human leukemia propagation is mediated by a rare quiescent label-retaining cell (LRC) population undetectable current immunophenotypic markers. AML quiescence reversible, preserving genetic clonal competition epigenetic...
NPM1-mutated acute myeloid leukemia (AML) is defined by aberrant cytoplasmic localization of the mutant NPM1c protein, and therapeutic strategies targeting this specific disease remain limited. Here, we identify TTLL4, a mono-glutamate glutamyltransferase, as selective vulnerability in AML. TTLL4 catalyzes post-translational hyper-glutamylation at E126, stabilizes its promotes differentiation block leukemic cells. Multiple genetic inactivation approaches human NPM1c-mutant cell lines reduce...
Abstract Many human cancers, including acute myeloid leukemia (AML), arise from mutations of stem and progenitor cells. Immunophenotypic profiling has shown that leukemias develop hierarchically, with in cells associated disease propagation relapse 1,2 . Although initiating can be enriched using cell surface markers, their frequency tends to variable low, obscuring mechanisms hindering effective therapies 3,4 To define AML patients, we performed functional genomic diverse label tracing...