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A line in shifting sand: Can we define and target TP53 mutated MDS?
Semin Hematol
December 2024
Division of Hematology and Oncology, Department of Medicine, The University of Pennsylvania, Philadelphia, PA. Electronic address:
Mutations in the tumor suppressor protein, TP53, lead to dismal outcomes in myeloid malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Recent pathological reclassifications have integrated TP53 mutated MDS and AML under a unified category of TP53 mutated myeloid neoplasms, which allows for more flexibility in treatment approaches. Therapeutic strategies have predominantly mirrored those for AML, with allogeneic stem cell transplantation emerging as critical for long-term disease control.
View Article and Find Full Text PDFConvergent epigenetic evolution drives relapse in acute myeloid leukemia.
Elife
April 2024
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States.
Relapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts and found that 40% of relapses occur without changes in driver mutations, suggesting that non-genetic mechanisms drive relapse in a large proportion of cases. We therefore characterized epigenetic patterns of AML relapse using 26 matched diagnosis-relapse samples with ATAC-seq.
View Article and Find Full Text PDFAgonist-induced functional analysis and cell sorting associated with single-cell transcriptomics characterizes cell subtypes in normal and pathological brain.
Genome Res
November 2020
Université Côte d'Azur, CNRS, Institute of Molecular Cellular Pharmacology, F-06560 Valbonne, France.
To gain better insight into the dynamic interaction between cells and their environment, we developed the agonist-induced functional analysis and cell sorting (aiFACS) technique, which allows the simultaneous recording and sorting of cells in real-time according to their immediate and individual response to a stimulus. By modulating the aiFACS selection parameters, testing different developmental times, using various stimuli, and multiplying the analysis of readouts, it is possible to analyze cell populations of any normal or pathological tissue. The association of aiFACS with single-cell transcriptomics allows the construction of functional tissue cartography based on specific pharmacological responses of cells.
View Article and Find Full Text PDFExcess dNTPs Trigger Oscillatory Surface Flow in the Early Drosophila Embryo.
Biophys J
May 2020
Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey; Lewis Sigler Institute of Integrative Genomics, Princeton University, Princeton, New Jersey; Department of Molecular Biology, Princeton University, Princeton, New Jersey; Center for Computational Biology, Flatiron Institute, New York, New York. Electronic address:
During the first 2 hours of Drosophila development, precisely orchestrated nuclear cleavages, cytoskeletal rearrangements, and directed membrane growth lead to the formation of an epithelial sheet around the yolk. The newly formed epithelium remains relatively quiescent during the next hour as it is patterned by maternal inductive signals and zygotic gene products. We discovered that this mechanically quiet period is disrupted in embryos with high levels of dNTPs, which have been recently shown to cause abnormally fast nuclear cleavages and interfere with zygotic transcription.
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