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SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia

Cuijuan Han, Alireza Khodadadi-Jamayran, Adam H. Lorch, Qi Jin, Valentina Serafin, Ping Zhu, Yuliya Politanska, Limin Sun, Blanca T. Gutierrez-Diaz, Marina Pryzhkova, et al.
(2022) SCIENCE ADVANCES. 8(3).
Author
Organization
Abstract
The production of noncanonical mRNA transcripts is associated with cell transformation. Driven by our previous findings on the sensitivity of T cell acute lymphoblastic leukemia (T-ALL) cells to SF3B1 inhibitors, we identified that SF3B1 inhibition blocks T-ALL growth in vivo with no notable associated toxicity. We also revealed protein stabilization of the U2 complex component SF3B1 via deubiquitination. Our studies showed that SF3B1 inhibition perturbs exon skipping, leading to nonsense-mediated decay and diminished levels of DNA damage response-related transcripts, such as the serine/threonine kinase CHEK2, and impaired DNA damage response. We also identified that SF3B1 inhibition leads to a general decrease in R-loop formation. We further demonstrate that clinically used SF3B1 inhibitors synergize with CHEK2 inhibitors and chemotherapeutic drugs to block leukemia growth. Our study provides the proof of principle for posttranslational regulation of splicing components and associated roles and therapeutic implications for the U2 complex in T cell leukemia.

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MLA
Han, Cuijuan, et al. “SF3B1 Homeostasis Is Critical for Survival and Therapeutic Response in T Cell Leukemia.” SCIENCE ADVANCES, vol. 8, no. 3, 2022, doi:10.1126/sciadv.abj8357.
APA
Han, C., Khodadadi-Jamayran, A., Lorch, A. H., Jin, Q., Serafin, V., Zhu, P., … Ntziachristos, P. (2022). SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia. SCIENCE ADVANCES, 8(3). https://doi.org/10.1126/sciadv.abj8357
Chicago author-date
Han, Cuijuan, Alireza Khodadadi-Jamayran, Adam H. Lorch, Qi Jin, Valentina Serafin, Ping Zhu, Yuliya Politanska, et al. 2022. “SF3B1 Homeostasis Is Critical for Survival and Therapeutic Response in T Cell Leukemia.” SCIENCE ADVANCES 8 (3). https://doi.org/10.1126/sciadv.abj8357.
Chicago author-date (all authors)
Han, Cuijuan, Alireza Khodadadi-Jamayran, Adam H. Lorch, Qi Jin, Valentina Serafin, Ping Zhu, Yuliya Politanska, Limin Sun, Blanca T. Gutierrez-Diaz, Marina Pryzhkova, Hiam Abdala-Valencia, Elizabeth Thomas Bartom, Barbara Buldini, Giuseppe Basso, Sadanandan E. Velu, Kavitha Sarma, Basil B. Mattamana, Byoung-Kyu Cho, Rebecca C. Obeng, Young Ah Goo, Philip W. Jordan, Aristotelis Tsirigos, Yalu Zhou, and Panagiotis Ntziachristos. 2022. “SF3B1 Homeostasis Is Critical for Survival and Therapeutic Response in T Cell Leukemia.” SCIENCE ADVANCES 8 (3). doi:10.1126/sciadv.abj8357.
Vancouver
1.
Han C, Khodadadi-Jamayran A, Lorch AH, Jin Q, Serafin V, Zhu P, et al. SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia. SCIENCE ADVANCES. 2022;8(3).
IEEE
[1]
C. Han et al., “SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia,” SCIENCE ADVANCES, vol. 8, no. 3, 2022.
@article{01GWQ5ZTGSPBY3NTGEESBR49RQ,
  abstract     = {{The production of noncanonical mRNA transcripts is associated with cell transformation. Driven by our previous findings on the sensitivity of T cell acute lymphoblastic leukemia (T-ALL) cells to SF3B1 inhibitors, we identified that SF3B1 inhibition blocks T-ALL growth in vivo with no notable associated toxicity. We also revealed protein stabilization of the U2 complex component SF3B1 via deubiquitination. Our studies showed that SF3B1 inhibition perturbs exon skipping, leading to nonsense-mediated decay and diminished levels of DNA damage response-related transcripts, such as the serine/threonine kinase CHEK2, and impaired DNA damage response. We also identified that SF3B1 inhibition leads to a general decrease in R-loop formation. We further demonstrate that clinically used SF3B1 inhibitors synergize with CHEK2 inhibitors and chemotherapeutic drugs to block leukemia growth. Our study provides the proof of principle for posttranslational regulation of splicing components and associated roles and therapeutic implications for the U2 complex in T cell leukemia.}},
  articleno    = {{eabj8357}},
  author       = {{Han, Cuijuan and  Khodadadi-Jamayran, Alireza and  Lorch, Adam H. and  Jin, Qi and  Serafin, Valentina and  Zhu, Ping and  Politanska, Yuliya and  Sun, Limin and  Gutierrez-Diaz, Blanca T. and  Pryzhkova, Marina and  Abdala-Valencia, Hiam and  Bartom, Elizabeth Thomas and  Buldini, Barbara and  Basso, Giuseppe and  Velu, Sadanandan E. and  Sarma, Kavitha and  Mattamana, Basil B. and  Cho, Byoung-Kyu and  Obeng, Rebecca C. and  Goo, Young Ah and  Jordan, Philip W. and  Tsirigos, Aristotelis and  Zhou, Yalu and Ntziachristos, Panagiotis}},
  issn         = {{2375-2548}},
  journal      = {{SCIENCE ADVANCES}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{14}},
  title        = {{SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia}},
  url          = {{http://doi.org/10.1126/sciadv.abj8357}},
  volume       = {{8}},
  year         = {{2022}},
}
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