The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins
Open accessAbstract
Mutations in genes encoding splicing factors (which we refer to as spliceosomal genes) are commonly found in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations recurrently affect specific amino acid residues, leading to perturbed normal splice site and exon recognition. Spliceosomal gene mutations are always heterozygous and rarely occur together with one another, suggesting that cells may tolerate only a partial deviation from normal splicing activity. To test this hypothesis, we engineered mice to express a mutated allele of serine/arginine-rich splicing factor 2 (Srsf2P95H)—which commonly occurs in individuals with MDS and AML—in an inducible, hemizygous manner in hematopoietic cells. These mice rapidly succumbed to fatal bone marrow failure, demonstrating that Srsf2-mutated cells depend on the wild-type Srsf2 allele for survival. In the context of leukemia, treatment with the spliceosome inhibitor E7107 (refs. 7,8) resulted in substantial reductions in leukemic burden, specifically in isogenic mouse leukemias and patient-derived xenograft AMLs carrying spliceosomal mutations. Whereas E7107 treatment of mice resulted in widespread intron retention and cassette exon skipping in leukemic cells regardless of Srsf2 genotype, the magnitude of splicing inhibition following E7107 treatment was greater in Srsf2-mutated than in Srsf2-wild-type leukemia, consistent with the differential effect of E7107 on survival. Collectively, these data provide genetic and pharmacologic evidence that leukemias with spliceosomal gene mutations are preferentially susceptible to additional splicing perturbations in vivo as compared to leukemias without such mutations. Modulation of spliceosome function may thus provide a new therapeutic avenue in genetically defined subsets of individuals with MDS or AML.
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Cites
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
Gene ontology analysis for RNA-seq: accounting for selection bias
Young, M. D., Wakefield, M. J., Smyth, G. K., & Oshlack, A. (2010) · Genome Biology · doi:10.1186/gb-2010-11-2-r14 · Cited by 7,107
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531
Frequent pathway mutations of splicing machinery in myelodysplasia
Yoshida, K., Sanada, M., Shiraishi, Y., Nowak, D., Nagata, Y., Yamamoto, R., Sato, Y., Sato-Otsubo, A., Kon, A., Nagasaki, M., et al. (2011) · Nature · doi:10.1038/nature10496 · Cited by 2,029
Age-related mutations associated with clonal hematopoietic expansion and malignancies
Xie, M., Lu, C., Wang, J., McLellan, M. D., Johnson, K. J., Wendl, M. C., McMichael, J. F., Schmidt, H. K., Yellapantula, V., Miller, C. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3733 · Cited by 1,874
Somatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts
Papaemmanuil, E., Cazzola, M., Boultwood, J., Malcovati, L., Vyas, P., Bowen, D., Pellagatti, A., Wainscoat, J. S., Hellstrom-Lindberg, E., Gambacorti-Passerini, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103283 · Cited by 1,222
SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition
Kim, E., Ilagan, J. O., Liang, Y., Daubner, G. M., Lee, S. C.-W., Ramakrishnan, A., Li, Y., Chung, Y. R., Micol, J.-B., Murphy, M. E., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.04.006 · Cited by 575
Self-citationMutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo
Shirai, C. L., Ley, J. N., White, B. S., Kim, S., Tibbitts, J., Shao, J., Ndonwi, M., Wadugu, B., Duncavage, E. J., Okeyo-Owuor, T., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.04.008 · Cited by 287
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Wang, E., Lu, S. X., Pastore, A., Chen, X., Imig, J., Chun-Wei Lee, S., Hockemeyer, K., Ghebrechristos, Y. E., Yoshimi, A., Inoue, D., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.01.010 · Cited by 338
Self-citationThe central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes
Sallman, D. A., & List, A. (2019) · Blood · doi:10.1182/blood-2018-10-844654 · Cited by 273
Synthetic Lethal and Convergent Biological Effects of Cancer-Associated Spliceosomal Gene Mutations
Lee, S. C.-W., North, K., Kim, E., Jang, E., Obeng, E., Lu, S. X., Liu, B., Inoue, D., Yoshimi, A., Ki, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.07.003 · Cited by 219
Self-citationHsieh, Y.-C., Guo, C., Yalamanchili, H. K., Abreha, M., Al-Ouran, R., Li, Y., Dammer, E. B., Lah, J. J., Levey, A. I., Bennett, D. A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.104 · Cited by 196
Metadata
- Authors
- Lee, S. C.-W., Dvinge, H., Kim, E., Cho, H., Micol, J.-B., Chung, Y. R., Durham, B. H., Yoshimi, A., Kim, Y. J., Thomas, M., Lobry, C., Chen, C.-W., Pastore, A., Taylor, J., Wang, X., Krivtsov, A., Armstrong, S. A., Palacino, J., Buonamici, S., Smith, P. G., Bradley, R. K., & Abdel-Wahab, O.
- Venue
- Nature Medicine
- Published
- 2016-05-02
- Volume
- 22
- Issue
- 6
- Pages
- 672-678
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2346030347
- Cited by
- 347
- References
- 10
- FWCI
- 22.72
- Type
- journal article
- Language
- en
- Open access
- green
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- Lee, S. C.-W., Dvinge, H., Kim, E., Cho, H., Micol, J.-B., Chung, Y. R., Durham, B. H., Yoshimi, A., Kim, Y. J., Thomas, M., Lobry, C., Chen, C.-W., Pastore, A., Taylor, J., Wang, X., Krivtsov, A., Armstrong, S. A., Palacino, J., Buonamici, S., . . . Abdel-Wahab, O. (2016). Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins. Nature Medicine. https://doi.org/10.1038/nm.4097
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