Lu, S. X., Wang, E., Pastore, A., Chen, X. F., Imig, J., Lee, S. C., Ghebrechristos, Y., Yoshimi, A., Bitner, L. E., Ki, M., Kloetgen, A., Lin, K. T., Tibes, R., Krainer, A. R., Uehara, T., Owa, T., Aifantis, I., Abdel-Wahab, O. I. (November 2018) Therapeutic Targeting of an RNA Splicing Factor Network for the Treatment of Myeloid Neoplasms. Blood, 132 (Supple). Meeting Abstract 427. ISSN 0006-4971
Abstract
RNA-binding proteins (RBPs) regulate many aspects of transcription and translation in a cell- and tissue-specific manner and are frequently dysregulated in malignancy. We systematically evaluated RBPs preferentially required in acute myeloid leukemia (AML) over other forms of cancer or normal hematopoietic precursors using a CRISPR/Cas9 domain-based, loss-of-function screen targeting 490 classical RBPs with 2,900 sgRNAs (Fig. A). This screen was performed in cells lines representing AML, T-cell acute lymphoblastic leukemia (T-ALL), and lung adenocarcinoma (LUAD) and revealed multiple RBPs preferentially required for AML survival, but not for T-ALL or LUAD survival. We identified genes encoding 21 RBPs that were >3-fold depleted in AML cells and significantly overexpressed in AML patient samples versus normal adult CD34+ precursors (p-value < 0.05; Fig. B).
| Item Type: | Paper |
|---|---|
| Subjects: | Publication Type > Meeting Abstract bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > RNA binding protein bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing |
| CSHL Authors: | |
| Communities: | CSHL labs > Krainer lab |
| Depositing User: | Matthew Dunn |
| Date: | 29 November 2018 |
| Date Deposited: | 25 Mar 2019 14:55 |
| Last Modified: | 25 Mar 2019 14:55 |
| URI: | https://repository.cshl.edu/id/eprint/37748 |
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