Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Exploring the oncogenic and therapeutic target potential of the MYB-TYK2 fusion gene in B-cell acute lymphoblastic leukemia

Cancer Gene Therapy volume 29, pages 1140–1152 (2022)Cite this article

Subjects

Abstract

TYK2-rearrangements have recently been identified in high-risk acute lymphoblastic leukemia (HR-ALL) cases and are associated with poor outcome. Current understanding of the leukemogenic potential and therapeutic targetability of activating TYK2 alterations in the ALL setting is unclear, thus further investigations are warranted. Consequently, we developed in vitro, and for the first time, in vivo models of B-cell ALL from a patient harboring the MYB-TYK2 fusion gene. These models revealed JAK/STAT signaling activation and the oncogenic potential of the MYB-TYK2 fusion gene in isolation. High throughput screening identified the HDAC inhibitor, vorinostat and the HSP90 inhibitor, tanespimycin plus the JAK inhibitor, cerdulatinib as the most effective agents against cells expressing the MYB-TYK2 alteration. Evaluation of vorinostat and cerdulatinib in pre-clinical models of MYB-TYK2-rearranged ALL demonstrated that both drugs exhibited anti-leukemic effects and reduced the disease burden in treated mice. Importantly, these findings indicate that activating TYK2 alterations can function as driver oncogenes rather than passenger or secondary events in disease development. In addition, our data provide evidence for use of vorinostat and cerdulatinib in the treatment regimens of patients with this rare yet aggressive type of high-risk ALL that warrants further investigation in the clinical setting.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The MYB-TYK2 fusion gene demonstrated transformative potential in in vitro models.
Fig. 2: Mice transplanted with cells expressing the MYB-TYK2 fusion gene developed leukemia with a median latency of 84 days.
Fig. 3: Heat map representation of potential IC50 of selected compounds in the secondary HTS.
Fig. 4: Vorinostat treatment significantly decreased the activation of JAK/STAT effector proteins, pSTAT5 and pSTAT3 in Ba/F3 cells expressing the MYB-TYK2 fusion gene.
Fig. 5: Cerdulatinib demonstrated efficacy against Ba/F3 MYB-TYK2 cells.
Fig. 6: The MYB-TYK2 mice treated with cerdulatinib and vorinostat exhibit reduced B-ALL burden.
Fig. 7: Cerdulatinib demonstrated synergy when used in combination with vorinostat or dexamethasone.

Similar content being viewed by others

References

  1. Roberts KG, Gu Z, Payne-Turner D, McCastlain K, Harvey RC, Chen IM, et al. High frequency and poor outcome of philadelphia chromosome-like acute lymphoblastic leukemia in adults. J Clin Oncol. 2017;35:394–401.

    Article  PubMed  Google Scholar 

  2. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7:e577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LA, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA. 2009;106:9414–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nguyen MH, Ho JM, Beattie BK, Barber DL. TEL-JAK2 mediates constitutive activation of the phosphatidylinositol 3’-kinase/protein kinase B signaling pathway. J Biol Chem. 2001;276:32704–13.

    Article  CAS  PubMed  Google Scholar 

  5. Vainchenker W, Constantinescu SN. JAK/STAT signaling in hematological malignancies. Oncogene. 2013;32:2601–13.

    Article  CAS  PubMed  Google Scholar 

  6. Roberts KG, Mullighan CG. Genomics in acute lymphoblastic leukaemia: insights and treatment implications. Nat Rev Clin Oncol. 2015;12:344–57.

    Article  CAS  PubMed  Google Scholar 

  7. Maude SL, Tasian SK, Vincent T, Hall JW, Sheen C, Roberts KG, et al. Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood. 2012;120:3510–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tasian SK, Teachey DT, Li Y, Shen F, Harvey RC, Chen IM, et al. Potent efficacy of combined PI3K/mTOR and JAK or ABL inhibition in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood. 2017;129:177–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Suryani S, Bracken LS, Harvey RC, Sia KC, Carol H, Chen IM, et al. Evaluation of the in vitro and in vivo efficacy of the JAK inhibitor AZD1480 against JAK-mutated acute lymphoblastic leukemia. Mol Cancer Ther. 2015;14:364–74.

    Article  CAS  PubMed  Google Scholar 

  10. Savino AM, Sarno J, Trentin L, Vieri M, Fazio G, Bardini M, et al. The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL. Leukemia. 2017;31:2365–75.

    Article  CAS  PubMed  Google Scholar 

  11. Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, et al. BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012;120:2843–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Roberts KG, Yang YL, Payne-Turner D, Lin W, Files JK, Dickerson K, et al. Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL. Blood Adv. 2017;1:1657–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ma X, Liu Y, Liu Y, Alexandrov LB, Edmonson MN, Gawad C, et al. Pan-cancer genome and transcriptome analyses of 1699 paediatric leukaemias and solid tumours. Nature. 2018;555:371–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sanda T, Tyner JW, Gutierrez A, Ngo VN, Glover J, Chang BH, et al. TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia. Cancer Discov. 2013;3:564–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Waanders E, Scheijen B, Jongmans MC, Venselaar H, van Reijmersdal SV, van Dijk AH, et al. Germline activating TYK2 mutations in pediatric patients with two primary acute lymphoblastic leukemia occurrences. Leukemia. 2017;31:821–8.

    Article  CAS  PubMed  Google Scholar 

  16. Tavakoli Shirazi P, Eadie LN, Heatley SL, White DL. TYK2 activating alterations in acute lymphoblastic leukemia: novel driver oncogenes with potential avenues for precision medicine? J Cancer Sci Clin Ther. 2021;5:201–19.

    Article  Google Scholar 

  17. Leitner NR, Witalisz-Siepracka A, Strobl B, Muller M. Tyrosine kinase 2—surveillant of tumours and bona fide oncogene. Cytokine. 2017;89:209–18.

    Article  CAS  PubMed  Google Scholar 

  18. Woss K, Simonovic N, Strobl B, Macho-Maschler S, Muller M. TYK2: an upstream kinase of STATs in cancer. Cancers. 2019;11:1728.

  19. O’Shea JJ, Holland SM, Staudt LM. JAKs and STATs in immunity, immunodeficiency, and cancer. N Engl J Med. 2013;368:161–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371:1005–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Velusamy T, Kiel MJ, Sahasrabuddhe AA, Rolland D, Dixon CA, Bailey NG, et al. A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders. Blood. 2014;124:3768–71.

    Article  CAS  PubMed  Google Scholar 

  22. Crescenzo R, Abate F, Lasorsa E, Tabbo F, Gaudiano M, Chiesa N, et al. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell. 2015;27:516–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tomasson MH, Xiang Z, Walgren R, Zhao Y, Kasai Y, Miner T, et al. Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia. Blood. 2008;111:4797–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tron AE, Keeton EK, Ye M, Casas-Selves M, Chen H, Dillman KS, et al. Next-generation sequencing identifies a novel ELAVL1-TYK2 fusion gene in MOLM-16, an AML cell line highly sensitive to the PIM kinase inhibitor AZD1208. Leuk Lymphoma. 2016;57:2927–9.

    Article  PubMed  Google Scholar 

  25. Poitras JL, Dal Cin P, Aster JC, Deangelo DJ, Morton CC. Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre-B acute lymphocytic leukemia. Genes Chromosomes Cancer. 2008;47:884–9.

    Article  CAS  PubMed  Google Scholar 

  26. Klempnauer KH, Sippel AE. Subnuclear localization of proteins encoded by the oncogene v-myb and its cellular homolog c-myb. Mol Cell Biol. 1986;6:62–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Behrmann I, Smyczek T, Heinrich PC, Schmitz-Van de Leur H, Komyod W, Giese B, et al. Janus kinase (Jak) subcellular localization revisited: the exclusive membrane localization of endogenous Janus kinase 1 by cytokine receptor interaction uncovers the Jak.receptor complex to be equivalent to a receptor tyrosine kinase. J Biol Chem. 2004;279:35486–93.

    Article  CAS  PubMed  Google Scholar 

  28. Dunlop EA, Tee AR. Mammalian target of rapamycin complex 1: signalling inputs, substrates and feedback mechanisms. Cell Signal. 2009;21:827–35.

    Article  CAS  PubMed  Google Scholar 

  29. Williams RT, Roussel MF, Sherr CJ. Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia. Proc Natl Acad Sci USA. 2006;103:6688–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mullighan CG, Williams RT, Downing JR, Sherr CJ. Failure of CDKN2A/B (INK4A/B-ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL. Genes Dev. 2008;22:1411–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Notta F, Mullighan CG, Wang JC, Poeppl A, Doulatov S, Phillips LA, et al. Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells. Nature. 2011;469:362–7.

    Article  CAS  PubMed  Google Scholar 

  32. Patton DT, Plumb AW, Abraham N. The survival and differentiation of pro-B and pre-B cells in the bone marrow is dependent on IL-7Ralpha Tyr449. J Immunol. 2014;193:3446–55.

    Article  CAS  PubMed  Google Scholar 

  33. Oki Y, Kelly KR, Flinn I, Patel MR, Gharavi R, Ma A, et al. CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial. Haematologica. 2017;102:1923–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Younes A, Berdeja JG, Patel MR, Flinn I, Gerecitano JF, Neelapu SS, et al. Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial. Lancet Oncol. 2016;17:622–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Li X, Su Y, Hege K, Madlambayan G, Edwards H, Knight T, et al. The HDAC and PI3K dual inhibitor CUDC-907 synergistically enhances the antileukemic activity of venetoclax in preclinical models of acute myeloid leukemia. Haematologica. 2021;106:1262–77.

    CAS  PubMed  Google Scholar 

  36. Talaei S, Mellatyar H, Asadi A, Akbarzadeh A, Sheervalilou R, Zarghami N. Spotlight on 17-AAG as an Hsp90 inhibitor for molecular targeted cancer treatment. Chem Biol Drug Des. 2019;93:760–86.

    Article  CAS  PubMed  Google Scholar 

  37. Bailly C. Cepharanthine: an update of its mode of action, pharmacological properties and medical applications. Phytomedicine. 2019;62:152956.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lengline E, Beldjord K, Dombret H, Soulier J, Boissel N, Clappier E. Successful tyrosine kinase inhibitor therapy in a refractory B-cell precursor acute lymphoblastic leukemia with EBF1-PDGFRB fusion. Haematologica. 2013;98:e146–8.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Weston BW, Hayden MA, Roberts KG, Bowyer S, Hsu J, Fedoriw G, et al. Tyrosine kinase inhibitor therapy induces remission in a patient with refractory EBF1-PDGFRB-positive acute lymphoblastic leukemia. J Clin Oncol. 2013;31:e413–6.

    Article  PubMed  Google Scholar 

  40. Khajapeer KV, Baskaran R. Hsp90 inhibitors for the treatment of chronic myeloid leukemia. Leuk Res Treat. 2015;2015:757694.

    Google Scholar 

  41. Hawkins LM, Jayanthan AA, Narendran A. Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on pediatric acute lymphoblastic leukemia (ALL) with respect to Bcr-Abl status and imatinib mesylate sensitivity. Pediatr Res. 2005;57:430–7.

    Article  CAS  PubMed  Google Scholar 

  42. Coffey G, Betz A, DeGuzman F, Pak Y, Inagaki M, Baker DC, et al. The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancer. J Pharm Exp Ther. 2014;351:538–48.

    Article  CAS  Google Scholar 

  43. Ma J, Xing W, Coffey G, Dresser K, Lu K, Guo A, et al. Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma. Oncotarget. 2015;6:43881–96.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Coffey GP, Feng J, Betz A, Pandey A, Birrell M, Leeds JM, et al. Cerdulatinib pharmacodynamics and relationships to tumor response following oral dosing in patients with relapsed/refractory B-cell malignancies. Clin Cancer Res. 2019;25:1174–84.

    Article  CAS  PubMed  Google Scholar 

  45. Flinn I, Hamlin PA, Strickland DK, Pandey A, Birrell M, Coffey G, et al. Phase 1 open-label dose escalation study of the dual SYK/JAK inhibitor cerdulatinib (PRT062070) in patients with relapsed/refractory B-cell malignancies: Safety profile and clinical activity. J Clin Oncol. 2015;33:8531.

    Article  Google Scholar 

  46. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2013;5:a008656.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Slee EA, Adrain C, Martin SJ. Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis. J Biol Chem. 2001;276:7320–6.

    Article  CAS  PubMed  Google Scholar 

  48. dos Santos NR, Ghysdael J. A transgenic mouse model for TEL-JAK2-induced B-cell lymphoma/leukemia. Leukemia. 2006;20:182–5.

    Article  PubMed  CAS  Google Scholar 

  49. Cuesta-Dominguez A, Ortega M, Ormazabal C, Santos-Roncero M, Galan-Diez M, Steegmann JL, et al. Transforming and tumorigenic activity of JAK2 by fusion to BCR: molecular mechanisms of action of a novel BCR-JAK2 tyrosine-kinase. PLoS One. 2012;7:e32451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Staerk J, Kallin A, Demoulin JB, Vainchenker W, Constantinescu SN. JAK1 and Tyk2 activation by the homologous polycythemia vera JAK2 V617F mutation: cross-talk with IGF1 receptor. J Biol Chem. 2005;280:41893–9.

    Article  CAS  PubMed  Google Scholar 

  51. Ragimbeau J, Dondi E, Vasserot A, Romero P, Uze G, Pellegrini S. The receptor interaction region of Tyk2 contains a motif required for its nuclear localization. J Biol Chem. 2001;276:30812–8.

    Article  CAS  PubMed  Google Scholar 

  52. Ram PA, Waxman DJ. Interaction of growth hormone-activated STATs with SH2-containing phosphotyrosine phosphatase SHP-1 and nuclear JAK2 tyrosine kinase. J Biol Chem. 1997;272:17694–702.

    Article  CAS  PubMed  Google Scholar 

  53. Wozniak MB, Villuendas R, Bischoff JR, Aparicio CB, Martinez Leal JF, de La Cueva P, et al. Vorinostat interferes with the signaling transduction pathway of T-cell receptor and synergizes with phosphoinositide-3 kinase inhibitors in cutaneous T-cell lymphoma. Haematologica. 2010;95:613–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem. 2007;282:20059–63.

    Article  CAS  PubMed  Google Scholar 

  55. Nusinzon I, Horvath CM. Unexpected roles for deacetylation in interferon- and cytokine-induced transcription. J Interferon Cytokine Res. 2005;25:745–8.

    Article  CAS  PubMed  Google Scholar 

  56. Buchwald M, Kramer OH, Heinzel T. HDACi-targets beyond chromatin. Cancer Lett. 2009;280:160–7.

    Article  CAS  PubMed  Google Scholar 

  57. Rascle A, Johnston JA, Amati B. Deacetylase activity is required for recruitment of the basal transcription machinery and transactivation by STAT5. Mol Cell Biol. 2003;23:4162–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sakamoto S, Potla R, Larner AC. Histone deacetylase activity is required to recruit RNA polymerase II to the promoters of selected interferon-stimulated early response genes. J Biol Chem. 2004;279:40362–7.

    Article  CAS  PubMed  Google Scholar 

  59. Klampfer L, Huang J, Swaby LA, Augenlicht L. Requirement of histone deacetylase activity for signaling by STAT1. J Biol Chem. 2004;279:30358–68.

    Article  CAS  PubMed  Google Scholar 

  60. Zhuang S. Regulation of STAT signaling by acetylation. Cell Signal. 2013;25:1924–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wang R, Cherukuri P, Luo J. Activation of Stat3 sequence-specific DNA binding and transcription by p300/CREB-binding protein-mediated acetylation. J Biol Chem. 2005;280:11528–34.

    Article  CAS  PubMed  Google Scholar 

  62. Yuan ZL, Guan YJ, Chatterjee D, Chin YE. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science. 2005;307:269–73.

    Article  CAS  PubMed  Google Scholar 

  63. Gupta M, Han JJ, Stenson M, Wellik L, Witzig TE. Regulation of STAT3 by histone deacetylase-3 in diffuse large B-cell lymphoma: implications for therapy. Leukemia. 2012;26:1356–64.

    Article  CAS  PubMed  Google Scholar 

  64. Tambaro FP, Dell’aversana C, Carafa V, Nebbioso A, Radic B, Ferrara F, et al. Histone deacetylase inhibitors: clinical implications for hematological malignancies. Clin Epigenet. 2010;1:25–44.

    Article  CAS  Google Scholar 

  65. Bocchini CE, Kasembeli MM, Roh SH, Tweardy DJ. Contribution of chaperones to STAT pathway signaling. JAKSTAT. 2014;3:e970459.

    PubMed  PubMed Central  Google Scholar 

  66. Prodromou C. Mechanisms of Hsp90 regulation. Biochem J. 2016;473:2439–52.

    Article  CAS  PubMed  Google Scholar 

  67. Schoof N, von Bonin F, Trumper L, Kube D. HSP90 is essential for Jak-STAT signaling in classical Hodgkin lymphoma cells. Cell Commun Signal. 2009;7:17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Kucine N, Marubayashi S, Bhagwat N, Papalexi E, Koppikar P, Sanchez Martin M, et al. Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias. Blood. 2015;126:2479–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Akahane K, Sanda T, Mansour MR, Radimerski T, DeAngelo DJ, Weinstock DM, et al. HSP90 inhibition leads to degradation of the TYK2 kinase and apoptotic cell death in T-cell acute lymphoblastic leukemia. Leukemia. 2016;30:219–28.

    Article  CAS  PubMed  Google Scholar 

  70. Gadina M, Johnson C, Schwartz D, Bonelli M, Hasni S, Kanno Y, et al. Translational and clinical advances in JAK-STAT biology: the present and future of jakinibs. J Leukoc Biol. 2018;104:499–514.

    Article  CAS  PubMed  Google Scholar 

  71. Vainchenker W, Leroy E, Gilles L, Marty C, Plo I, Constantinescu SN. JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders. F1000 Res. 2018;7:82.

    Article  CAS  Google Scholar 

  72. Ebadi M, Wasko J, Weisdorf DJ, Gordon PM, Rashidi A. Ruxolitinib combined with chemotherapy can eradicate chemorefractory central nervous system acute lymphoblastic leukaemia. Br J Haematol. 2019;187:e24–e7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Funding of this study was provided by National Health and Medical Research Council, Cancer Council Beat Cancer Project and the Leukaemia Foundation Australia. PT was supported by an AGR University of Adelaide scholarship and Betty Hartmann Leukaemia Research Supplementary Scholarship. Flow cytometry analysis and cell sorting were performed at the South Australian Health Medical Research Institute (SAHMRI) in the ACRF Cellular Imaging and Cytometry Core Facility. The Facility is generously supported by the Detmold Hoopman Group, Australian Cancer Research Foundation and Australian Government through the Zero Childhood Cancer Program. Animal models were performed in the Bioresources Core Facility at SAHMRI and we would like to acknowledge the technical support provided. HTS was performed at Cell Screen SA, Flinders Centre for Innovation in Cancer and we would like to thank Dr. Amanda Aloia and Dr. Bracho Granado for assisting with assay optimization. We would like to thank Prof. Charles Mullighan for provision of the MYB-TYK2 construct.

Author information

Authors and Affiliations

  1. Cancer Program, Precision Medicine Theme, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, SA, Australia

    Paniz Tavakoli Shirazi, Laura N. Eadie, Susan L. Heatley, Elyse C. Page, Timothy P. Hughes, David Yeung & Deborah L. White

  2. Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia

    Paniz Tavakoli Shirazi, Laura N. Eadie, Susan L. Heatley, Timothy P. Hughes, David Yeung & Deborah L. White

  3. Faculty of Sciences, University of Adelaide, Adelaide, SA, Australia

    Maxime François & Deborah L. White

  4. CSIRO Health and Biosecurity, Nutrition & Health Program, Adelaide, SA, Australia

    Maxime François

  5. Royal Adelaide Hospital, Adelaide, SA, Australia

    Timothy P. Hughes & David Yeung

  6. Australian Genomics Health Alliance (AGHA), Parkville, VIC, Australia

    Deborah L. White

Authors
  1. Paniz Tavakoli Shirazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura N. Eadie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susan L. Heatley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elyse C. Page
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maxime François
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Timothy P. Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David Yeung
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Deborah L. White
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PT conceived the study, performed the experiments, analyzed the data and wrote the manuscript. LE contributed to the study design. MF and EP helped in performing the experiments. LE, SH, and DW supervised the research. All authors critically read and revised the manuscript.

Corresponding author

Correspondence to Deborah L. White.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shirazi, P.T., Eadie, L.N., Heatley, S.L. et al. Exploring the oncogenic and therapeutic target potential of the MYB-TYK2 fusion gene in B-cell acute lymphoblastic leukemia. Cancer Gene Ther 29, 1140–1152 (2022). https://doi.org/10.1038/s41417-021-00421-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41417-021-00421-6

This article is cited by

Search

Advanced search

Quick links