Proceedings of the National Academy of Sciences · 2019 · 68 citations · 50 references
MedicineOncologyPharmacologyChemotherapyMolecular OncologyTranscriptomicsCancer TranscriptomicsMolecular Tumor ProfilingNext-generation Sequencing In OncologyTranscriptomic HeterogeneityTranscriptomic ProfilingTumor ClassificationAcute Leukemia ChemotherapyAcute Myeloid Leukemia BiologyAcute Myeloid Leukemia TherapyCytogenetic Prognostic MarkersLeukemia ClassificationRefractory Acute Myeloid LeukemiaRna SequencingRna Sequencing (Rna-seq)
= 131), was prognostic for overall survival (OS) and refined an established 17-gene stemness score. Refractory subpopulations have differential expression in pathways involved in cell cycle, transcription, translation, metabolism, and/or stem cell properties. Ex vivo drug sensitivity to 122 small-molecule inhibitors revealed effective group-specific targeting of pathways among these three refractory groups. Gene expression profiling by RNA sequencing had a suboptimal ability to correctly predict those individuals resistant to conventional cytotoxic induction therapy, but could risk-stratify for OS and identify subjects most likely to have superior responses to a specific alternative therapy. Such personalized therapy may be studied prospectively in clinical trials.
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