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- W3206893004 abstract "Abstract Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed targeted DNA sequencing as well as transcriptional and proteomic profiling of paired leukemia-infiltrating cells in the bone marrow (BM) and CNS of xenografts. Genes governing mRNA translation were upregulated in CNS leukemia, and subclonal genetic profiling confirmed this in both BM-concordant and BM-discordant CNS mutational populations. CNS leukemia cells were exquisitely sensitive to the translation inhibitor omacetaxine mepesuccinate, which reduced xenograft leptomeningeal disease burden. Proteomics demonstrated greater abundance of secreted proteins in CNS-infiltrating cells, including complement component 3 (C3), and drug targeting of C3 influenced CNS disease in xenografts. CNS-infiltrating cells also exhibited selection for stemness traits and metabolic reprogramming. Overall, our study identifies targeting of mRNA translation as a potential therapeutic approach for B-ALL leptomeningeal disease. Significance: Cancer metastases are often driven by distinct subclones with unique biological properties. Here we show that in B-ALL CNS disease, the leptomeningeal environment selects for cells with unique functional dependencies. Pharmacologic inhibition of mRNA translation signaling treats CNS disease and offers a new therapeutic approach for this condition. This article is highlighted in the In This Issue feature, p. 1" @default.
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- W3206893004 date "2021-10-11" @default.
- W3206893004 modified "2023-10-14" @default.
- W3206893004 title "Multiomic Profiling of Central Nervous System Leukemia Identifies mRNA Translation as a Therapeutic Target" @default.
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- W3206893004 cites W1980932232 @default.
- W3206893004 cites W1994302475 @default.
- W3206893004 cites W2008271309 @default.
- W3206893004 cites W2023728706 @default.
- W3206893004 cites W2024224952 @default.
- W3206893004 cites W2031371243 @default.
- W3206893004 cites W2035151737 @default.
- W3206893004 cites W2040329520 @default.
- W3206893004 cites W2040885133 @default.
- W3206893004 cites W2052001124 @default.
- W3206893004 cites W2070040136 @default.
- W3206893004 cites W2080752012 @default.
- W3206893004 cites W2082409119 @default.
- W3206893004 cites W2083465317 @default.
- W3206893004 cites W2096173332 @default.
- W3206893004 cites W2114104545 @default.
- W3206893004 cites W2118272259 @default.
- W3206893004 cites W2130410032 @default.
- W3206893004 cites W2132079316 @default.
- W3206893004 cites W2134526812 @default.
- W3206893004 cites W2138487969 @default.
- W3206893004 cites W2142908878 @default.
- W3206893004 cites W2159675211 @default.
- W3206893004 cites W2169456326 @default.
- W3206893004 cites W2169589032 @default.
- W3206893004 cites W2255229856 @default.
- W3206893004 cites W2269933663 @default.
- W3206893004 cites W2337451127 @default.
- W3206893004 cites W2345262650 @default.
- W3206893004 cites W2431835570 @default.
- W3206893004 cites W2461732257 @default.
- W3206893004 cites W2526338590 @default.
- W3206893004 cites W2528101941 @default.
- W3206893004 cites W2536237561 @default.
- W3206893004 cites W2543449938 @default.
- W3206893004 cites W2545964391 @default.
- W3206893004 cites W2557535757 @default.
- W3206893004 cites W2591646072 @default.
- W3206893004 cites W2606545518 @default.
- W3206893004 cites W2613468286 @default.
- W3206893004 cites W2618999154 @default.
- W3206893004 cites W2625763766 @default.
- W3206893004 cites W2728037575 @default.
- W3206893004 cites W2773927148 @default.
- W3206893004 cites W2793800931 @default.
- W3206893004 cites W2883104324 @default.
- W3206893004 cites W2889395887 @default.
- W3206893004 cites W2913580720 @default.
- W3206893004 cites W2938451492 @default.
- W3206893004 cites W2966662961 @default.
- W3206893004 cites W2982426375 @default.
- W3206893004 cites W2984202283 @default.
- W3206893004 cites W3000584534 @default.
- W3206893004 cites W3004434748 @default.
- W3206893004 cites W3008763686 @default.
- W3206893004 cites W3021539898 @default.
- W3206893004 cites W3025103340 @default.
- W3206893004 cites W3091416909 @default.
- W3206893004 cites W3091607301 @default.
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- W3206893004 doi "https://doi.org/10.1158/2643-3230.bcd-20-0216" @default.
- W3206893004 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35019858" @default.
- W3206893004 hasPublicationYear "2021" @default.
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