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Original Research

Analysis of RBP expression and binding sites identifies PTBP1 as a regulator of CD19 expression in B-ALL

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Article: 2184143 | Received 02 Sep 2022, Accepted 20 Feb 2023, Published online: 01 Mar 2023

References

  • Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–12. doi:10.1056/NEJMoa1407222.
  • Park JH, Riviere I, Gonen M, Wang X, Senechal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E, et al. Long-term follow-up of CD19 CAR therapy in Acute Lymphoblastic Leukemia. N Engl J Med. 2018;378(5):449–459. doi:10.1056/NEJMoa1709919.
  • Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11(4):69 (2021). doi:10.1038/s41408-021-00459-7.
  • Shah NN, Fry TJ. Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol. 2019;16(6):372–385. doi:10.1038/s41571-019-0184-6.
  • Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, et al. Tisagenlecleucel in children and young adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018;378(5):439–448. doi:10.1056/NEJMoa1709866.
  • Xu X, Sun Q, Liang X, Chen Z, Zhang X, Zhou X, Li M, Tu H, Liu Y, Tu S et al. Mechanisms of relapse after CD19 CAR T-cell therapy for acute Lymphoblastic Leukemia and its prevention and treatment Strategies. Front Immunol. 2019;10:2664. doi:10.3389/fimmu.2019.02664.
  • Guo Z, Tu S, Yu S, Wu L, Pan W, Chang N, Zhou X, Song C, Li Y, He Y, et al. Preclinical and clinical advances in dual-target chimeric antigen receptor therapy for hematological malignancies. Cancer Sci 2021;01(9ed2021):1357–1368. doi:10.1111/cas.14799.
  • Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, Wolters P, Martin S, Delbrook C, Yates B, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018;24(1):20–28. doi:10.1038/nm.4441.
  • Spiegel JY, Patel S, Muffly L, Hossain NM, Oak J, Baird JH, Frank MJ, Shiraz P, Sahaf B, Craig J, et al. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021;27(8):1419–1431. doi:10.1038/s41591-021-01436-0.
  • Shah NN, Johnson BD, Schneider D, Zhu F, Szabo A, Keever-Taylor CA, Krueger W, Worden AA, Kadan MJ, Yim S, et al. Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. Nat Med. 2020;26(10):1569–1575. doi:10.1038/s41591-020-1081-3.
  • Larson SMW, Ji CM, Ghafouri B, Naparstek SN, Trent, J J. CD19/CD20 bispecific chimeric antigen receptor (CAR) in naïve/memory T cells for the treatment of relapsed or refractory non-hodgkin lymphoma. Cancer Discov. 2022;13:1–18. doi:10.1158/2159-8290.CD-22-0964.
  • Orlando EJ, Han X, Tribouley C, Wood PA, Leary RJ, Riester M, Levine JE, Qayed M, Grupp SA, Boyer M, et al. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat Med. 2018;24(10):1504–1506. doi:10.1038/s41591-018-0146-z.
  • Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, Sussman R, Lanauze C, Ruella M, Gazzara MR, et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015;5(12):1282–1295. doi:10.1158/2159-8290.CD-15-1020.
  • Asnani M, Hayer KE, Naqvi AS, Zheng S, Yang SY, Oldridge D, Ibrahim F, Maragkakis M, Gazzara MR, Black KL, et al. Retention of CD19 intron 2 contributes to CART-19 resistance in leukemias with subclonal frameshift mutations in CD19. Leukemia. 2020;34(4):1202–1207. doi:10.1038/s41375-019-0580-z.
  • Bagashev A, Sotillo E, Tang CH, Black KL, Perazzelli J, Seeholzer SH, Argon Y, Barrett DM, Grupp SA, Hu CC, et al. CD19 alterations emerging after CD19-directed immunotherapy cause retention of the Misfolded protein in the endoplasmic reticulum. Mol Cell Biol. 2018;38(21):21. doi:10.1128/MCB.00383-18.
  • Rabilloud T, Potier D, Pankaew S, Nozais M, Loosveld M, Payet-Bornet D. Single-cell profiling identifies pre-existing CD19-negative subclones in a B-ALL patient with CD19-negative relapse after CAR-T therapy. Nat Commun. 2021;12:865.
  • Fischer J, Paret C, El Malki K, Alt F, Wingerter A, Neu MA, Kron B, Russo A, Lehmann N, Roth L, et al. CD19 Isoforms enabling Resistance to CART-19 immunotherapy are expressed in B-ALL patients at initial diagnosis. J Immunother. 2017;40(5):187–195. doi:10.1097/CJI.0000000000000169.
  • Cortés-López M, Schulz L, Enculescu M, Paret C, Spiekermann B, Quesnel-Vallières M, Torres-Diz M, Unic S, Busch A, Orekhova A, et al. High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance. Nat Commun. 2022;13(1). doi:10.1038/s41467-022-31818-y.
  • Giudice G, Sanchez-Cabo F, Torroja C, Lara-Pezzi E. ATtRACT-a database of RNA-binding proteins and associated motifs. Database (Oxford). 2016;2016:baw035. doi:10.1093/database/baw035.
  • Robinson JT, Thorvaldsdottir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP. Integrative genomics viewer. Nat Biotechnol. 2011;29(1):24–26. doi:10.1038/nbt.1754.
  • McLeod C, Gout AM, Zhou X, Thrasher A, Rahbarinia D, Brady SW, Macias M, Birch K, Finkelstein D, Sunny J, et al. St. jude cloud: a pediatric cancer genomic data-sharing ecosystem. Cancer Discov. 2021;11(5):1082–1099. doi:10.1158/2159-8290.CD-20-1230.
  • Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. doi:10.1186/s13059-014-0550-8.
  • Stephens M. False discovery rates: a new deal. Biostatistics. 2017;18(2):275–294. doi:10.1093/biostatistics/kxw041.
  • Perez I, Lin CH, McAfee JG, Patton JG. Mutation of PTB binding sites causes misregulation of alternative 3’ splice site selection in vivo. RNA. 1997;3:764–778.
  • Feng H, Bao S, Rahman MA, Weyn-Vanhentenryck SM, Khan A, Wong J, Shah A, Flynn ED, Krainer AR, Zhang C, et al. Modeling RNA-binding protein specificity in vivo by precisely registering protein-RNA crosslink sites. Mol Cell. 2019;74(6):1189–204 e6. doi:10.1016/j.molcel.2019.02.002.
  • Dominguez D, Freese P, Alexis MS, Su A, Hochman M, Palden T, Bazile C, Lambert NJ, Van Nostrand EL, Pratt GA, et al. Sequence, structure, and context preferences of human RNA binding proteins. Mol Cell. 2018;06(9ed2018):854–67 e9. doi:10.1016/j.molcel.2018.05.001.
  • Han A, Stoilov P, Linares AJ, Zhou Y, Fu XD, Black DL, Guigo R. De novo prediction of PTBP1 binding and splicing targets reveals unexpected features of its RNA recognition and function. PLoS Comput Biol. 2014;10(1):e1003442. doi:10.1371/journal.pcbi.1003442.
  • Amir-Ahmady B, Boutz PL, Markovtsov V, Phillips ML, Black DL. Exon repression by polypyrimidine tract binding protein. RNA. 2005;11(5):699–716. doi:10.1261/rna.2250405.
  • Mukherjee N, Jacobs NC, Hafner M, Kennington EA, Nusbaum JD, Tuschl T, Blackshear PJ, Ohler U. Global target mRNA specification and regulation by the RNA-binding protein ZFP36. Genome Biol. 2014;15(1):R12. doi:10.1186/gb-2014-15-1-r12.
  • Spellman R, Llorian M, Smith CW. Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Mol Cell. 2007;27(3):420–434. doi:10.1016/j.molcel.2007.06.016.
  • Jung H, Lee D, Lee J, Park D, Kim YJ, Park WY, Hong D, Park PJ, Lee E. Intron retention is a widespread mechanism of tumor-suppressor inactivation. Nat Genet. 2015;47(11):1242–1248. doi:10.1038/ng.3414.
  • Supek F, Minana B, Valcarcel J, Gabaldon T, Lehner B. Synonymous mutations frequently act as driver mutations in human cancers. Cell. 2014;156(6):1324–1335. doi:10.1016/j.cell.2014.01.051.
  • Darman RB, Seiler M, Agrawal AA, Lim KH, Peng S, Aird D, Bailey SL, Bhavsar EB, Chan B, Colla S, et al. Cancer-associated SF3B1 hotspot mutations induce cryptic 3’ splice site selection through use of a different branch point. Cell Rep. 2015;13(5):1033–1045. doi:10.1016/j.celrep.2015.09.053.
  • Quesada V, Conde L, Villamor N, Ordonez GR, Jares P, Bassaganyas L, Ramsay AJ, Beà S, Pinyol M, Martínez-Trillos A, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet. 2011;44(1):47–52. doi:10.1038/ng.1032.
  • Climente-Gonzalez H, Porta-Pardo E, Godzik A, Eyras E. The functional impact of alternative splicing in cancer. Cell Rep. 2017;20(9):2215–2226. doi:10.1016/j.celrep.2017.08.012.
  • Peng Q, Zhou Y, Oyang L, Wu N, Tang Y, Su M, Luo X, Wang Y, Sheng X, Ma J, et al. Impacts and mechanisms of alternative mRNA splicing in cancer metabolism, immune response, and therapeutics. Mol Ther. 2021;11:19ed2021.
  • Oberstrass FC, Auweter SD, Erat M, Hargous Y, Henning A, Wenter P, Reymond L, Amir-Ahmady B, Pitsch S, Black DL, et al. Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science. 2005;309(5743):2054–2057. doi:10.1126/science.1114066.
  • Galloway A, Saveliev A, Lukasiak S, Hodson DJ, Bolland D, Balmanno K, Ahlfors H, Monzón-Casanova E, Mannurita SC, Bell LS, et al. RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. Science. 2016;352(6284):453–459. doi:10.1126/science.aad5978.
  • Zekavati A, Nasir A, Alcaraz A, Aldrovandi M, Marsh P, Norton JD, Murphy JJ. Post-transcriptional regulation of BCL2 mRNA by the RNA-binding protein ZFP36L1 in malignant B cells. PLoS One. 2014;9(7):e102625. doi:10.1371/journal.pone.0102625.
  • Newman R, Ahlfors H, Saveliev A, Galloway A, Hodson DJ, Williams R, Besra GS, Cook CN, Cunningham AF, Bell SE, et al. Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1. Nat Immunol. 2017;18(6):683–693. doi:10.1038/ni.3724.
  • Monzon-Casanova E, Matheson LS, Tabbada K, Zarnack K, Smith CW, Turner M. Polypyrimidine tract-binding proteins are essential for B cell development. Elife. 2020;9. doi:10.7554/eLife.53557.
  • Monzon-Casanova E, Screen M, Diaz-Munoz MD, Coulson RMR, Bell SE, Lamers G, Solimena M, Smith CWJ, Turner M. The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers. Nat Immunol. 2018;19(3):267–278. doi:10.1038/s41590-017-0035-5.
  • Black KL, Naqvi AS, Asnani M, Hayer KE, Yang SY, Gillespie E, Bagashev A, Pillai V, Tasian SK, Gazzara MR, et al. Aberrant splicing in B-cell acute lymphoblastic leukemia. Nucleic Acids Res. 2018;46(21):11357–11369. doi:10.1093/nar/gky946.
  • Xiao W, Adhikari S, Dahal U, Chen YS, Hao YJ, Sun BF, Sun H-Y, Li A, Ping X-L, Lai W-Y, et al. Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. Mol Cell. 2016;61(4):507–519. doi:10.1016/j.molcel.2016.01.012.
  • Katsuyama T, Moulton VR. Splicing factor SRSF1 is indispensable for regulatory T cell homeostasis and function. Cell Rep. 2021;36(1):109339. doi:10.1016/j.celrep.2021.109339.
  • Diaz-Munoz MD, Osma-Garcia IC. The RNA regulatory programs that govern lymphocyte development and function. Wiley Interdiscip Rev RNA. 2021;13(1):e1683. doi:10.1002/wrna.1683.
  • Diaz-Munoz MD, Turner M. Uncovering the role of RNA-binding proteins in gene expression in the immune system. Front Immunol. 2018;9:1094. doi:10.3389/fimmu.2018.01094.
  • Turner M, Diaz-Munoz MD. RNA-binding proteins control gene expression and cell fate in the immune system. Nat Immunol. 2018;01(20ed2018):120–129. doi:10.1038/s41590-017-0028-4.
  • Keene JD. RNA regulons: coordination of post-transcriptional events. Nat Rev Genet. 2007;8(7):533–543. doi:10.1038/nrg2111.
  • Guo J, Jia J, Jia R. PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells. Sci Rep. 2015;5(1):14548. doi:10.1038/srep14548.
  • Zhou Z, Gong Q, Lin Z, Wang Y, Li M, Wang L, Ding H, Li P. Emerging Roles of SRSF3 as a Therapeutic Target for Cancer. Front Oncol. 2020;10:577636. doi:10.3389/fonc.2020.577636.
  • Izquierdo JM, Majos N, Bonnal S, Martinez C, Castelo R, Guigo R, Bilbao D, Valcárcel J. Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition. Mol Cell. 2005;19(4):475–484. doi:10.1016/j.molcel.2005.06.015.
  • Downing JR, Wilson RK, Zhang J, Mardis ER, CH P, Ding L, Ley TJ, Evans WE. The Pediatric Cancer Genome Project. Nat Genet. 2012;44(6):619–622. doi:10.1038/ng.2287.
  • Newman S, Nakitandwe J, Kesserwan CA, Azzato EM, Wheeler DA, Rusch M, Shurtleff S, Hedges DJ, Hamilton KV, Foy SG, et al. Genomes for kids: the scope of pathogenic mutations in pediatric cancer revealed by comprehensive DNA and RNA sequencing. Cancer Discov. 2021;11(12):3008–3027. doi:10.1158/2159-8290.CD-20-1631.
  • Rusch M, Nakitandwe J, Shurtleff S, Newman S, Zhang Z, Edmonson MN, Parker M, Jiao Y, Ma X, Liu Y, et al. Clinical cancer genomic profiling by three-platform sequencing of whole genome, whole exome and transcriptome. Nat Commun. 2018;9(1):3962. doi:10.1038/s41467-018-06485-7.
  • Alexander TB, Gu Z, Iacobucci I, Dickerson K, Choi JK, Xu B, Payne-Turner D, Yoshihara H, Loh ML, Horan J, et al. The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature. 2018;562(7727):373–379. doi:10.1038/s41586-018-0436-0.
  • Andersson AK, Ma J, Wang J, Chen X, Gedman AL, Dang J, Nakitandwe J, Holmfeldt L, Parker M, Easton J, et al. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nat Genet. 2015;47(4):330–337. doi:10.1038/ng.3230.
  • Gu Z, Churchman ML, Roberts KG, Moore I, Zhou X, Nakitandwe J, Hagiwara K, Pelletier S, Gingras S, Berns H, et al. PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia. Nat Genet. 2019;51(2):296–307. doi:10.1038/s41588-018-0315-5.
  • Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, Ding L, Lu C, Song G, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005–1015. doi:10.1056/NEJMoa1403088.