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• W3016990807 abstract "Abstract Infants with MLL -rearranged acute lymphoblastic leukemia (ALL) undergo intense therapy to counter a highly aggressive leukemia with survival rates of only 30-40%. The majority of patients initially show therapy response, but in two-thirds of cases the leukemia returns, typically during treatment. Accurate relapse prediction would enable treatment strategies that take relapse risk into account, with potential benefits for all patients. Through analysis of diagnostic bone marrow biopsies, we show that single-cell RNA sequencing can predict future relapse occurrence. By analysing gene modules derived from an independent study of the gene expression response to the key drug prednisone, individual leukemic cells are predicted to be either resistant or sensitive to treatment. Quantification of the proportion of cells classified by single-cell transcriptomics as resistant or sensitive, accurately predicts the occurrence of future relapse in individual patients. Strikingly, the single-cell based classification is even consistent with the order of relapse timing. These results lay the foundation for risk-based treatment of MLL -rearranged infant ALL, through single-cell classification. This work also sheds light on the subpopulation of cells from which leukemic relapse arises. Leukemic cells associated with high relapse risk are characterized by a smaller size and a quiescent gene expression program. These cells have significantly fewer transcripts, thereby also demonstrating why single-cell analyses may outperform bulk mRNA studies for risk stratification. This study indicates that single-cell RNA sequencing will be a valuable tool for risk stratification of MLL -rearranged infant ALL, and shows how clinically relevant information can be derived from single-cell genomics. Key Points Single-cell RNA sequencing accurately predicts relapse in MLL -rearranged infant ALL Identification of cells from which MLL -rearranged infant ALL relapses occur" @default.
• W3016990807 created "2020-04-24" @default.
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• W3016990807 date "2020-04-17" @default.
• W3016990807 modified "2023-09-24" @default.
• W3016990807 title "Single-cell transcriptomics predicts relapse in MLL-rearranged acute lymphoblastic leukemia in infants" @default.
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• W3016990807 doi "https://doi.org/10.1101/2020.04.14.20056580" @default.
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