The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status

Ricky M. Trigg; Liam C. Lee; Nina Prokoph; Leila Jahangiri; C. Patrick Reynolds; G. A. Amos Burke; Nicola A. Probst; Miaojun Han; Jamie D. Matthews; Hong Kai Lim; Eleanor Manners; Sonia Martinez; Joaquin Pastor; Carmen Blanco-Aparicio; Olaf Merkel; Ines Garces de los Fayos Alonso; Petra Kodajova; Simone Tangermann; Sandra Högler; Ji Luo; Lukas Kenner; Suzanne D. Turner

doi:10.1038/s41467-019-13315-x

The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status

Ricky M. Trigg, Liam C. Lee, Nina Prokoph, Leila Jahangiri, C. Patrick Reynolds, G. A. Amos Burke, Nicola A. Probst, Miaojun Han, Jamie D. Matthews, Hong Kai Lim, Eleanor Manners, Sonia Martinez, Joaquin Pastor, Carmen Blanco-Aparicio, Olaf Merkel, Ines Garces de los Fayos Alonso, Petra Kodajova, Simone Tangermann, Sandra Högler, Ji LuoLukas Kenner, Suzanne D. Turner^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

34 Citations (SciVal)

Original language	English
Article number	5428
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13315-x
Publication status	Published (VoR) - 1 Dec 2019

Funding

4Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. 5Department of Experimental Pathology and Laboratory Animal Pathology, Institute of Clinical Pathology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna 1090, Austria. 6Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Veterinärplatz 1, Vienna 1210, Austria. 7Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA. 8Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Boltzmanngasse 20, Medical University of Vienna, Vienna 1090, Austria. 9Present address: Functional Genomics, Medicinal Science & Technology, GlaxoSmithKline, Stevenage SG1 2NY, UK. 10Present address: Amgen, Thousand Oaks, CA 91320, USA. 11Present address: OncoSec, San Diego, CA 92121, USA. 12These authors contributed equally: Ricky M. Trigg, Liam C. Lee, Nina Prokoph, Lukas Kenner, Suzanne D. Turner. *email: [email protected] This research is supported with funding from Children with Cancer UK (CWCUK; 16-209) awarded to S.D.T. and L.C.L., R.M.T. was supported by the CWCUK grant and L.C.L. was in receipt of a Cancer Research UK Cambridge Centre Paediatric Programme PhD studentship. N.P., L.J., O.M., I.G.F.A., L.K. and S.D.T. are supported by a European Union Horizon 2020 Marie Skłodowska–Curie Innovative Training Networks (ITN-ETN) Grant, Grant No.: 675712. N.A.P. was supported by ERASMUS+. We are grateful to AstraZeneca for providing us with AZD1208 and Inflection Biosciences for providing us with PIMi. We thank Isaia Barbieri for critical suggestions on the manuscript, BBSCR NIHR Cell phenotyping hub for flow cytometry expertise, the Bauer Core Facility at Harvard University for sequencing, and Liew Jun Mun and Stephen P. Ducray for technical assistance. Funding for the COG/ALSF Childhood Cancer Repository was provided by Alex’s Lemonade Stand Foundation.

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Trigg, R. M., Lee, L. C., Prokoph, N., Jahangiri, L., Reynolds, C. P., Amos Burke, G. A., Probst, N. A., Han, M., Matthews, J. D., Kai Lim, H., Manners, E., Martinez, S., Pastor, J., Blanco-Aparicio, C., Merkel, O., de los Fayos Alonso, I. G., Kodajova, P., Tangermann, S., Högler, S., ... Turner, S. D. (2019). The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status. Nature Communications, 10(1), Article 5428. https://doi.org/10.1038/s41467-019-13315-x

@article{0b71b9ae362b48edab5b816065a0837a,

title = "The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status",

author = "Trigg, \{Ricky M.\} and Lee, \{Liam C.\} and Nina Prokoph and Leila Jahangiri and Reynolds, \{C. Patrick\} and \{Amos Burke\}, \{G. A.\} and Probst, \{Nicola A.\} and Miaojun Han and Matthews, \{Jamie D.\} and \{Kai Lim\}, Hong and Eleanor Manners and Sonia Martinez and Joaquin Pastor and Carmen Blanco-Aparicio and Olaf Merkel and \{de los Fayos Alonso\}, \{Ines Garces\} and Petra Kodajova and Simone Tangermann and Sandra H{\"o}gler and Ji Luo and Lukas Kenner and Turner, \{Suzanne D.\}",

note = "Funding Information: 4Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. 5Department of Experimental Pathology and Laboratory Animal Pathology, Institute of Clinical Pathology, Medical University of Vienna, W{\"a}hringer G{\"u}rtel 18-20, Vienna 1090, Austria. 6Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Veterin{\"a}rplatz 1, Vienna 1210, Austria. 7Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA. 8Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Boltzmanngasse 20, Medical University of Vienna, Vienna 1090, Austria. 9Present address: Functional Genomics, Medicinal Science \& Technology, GlaxoSmithKline, Stevenage SG1 2NY, UK. 10Present address: Amgen, Thousand Oaks, CA 91320, USA. 11Present address: OncoSec, San Diego, CA 92121, USA. 12These authors contributed equally: Ricky M. Trigg, Liam C. Lee, Nina Prokoph, Lukas Kenner, Suzanne D. Turner. *email: [email protected] Funding Information: This research is supported with funding from Children with Cancer UK (CWCUK; 16-209) awarded to S.D.T. and L.C.L., R.M.T. was supported by the CWCUK grant and L.C.L. was in receipt of a Cancer Research UK Cambridge Centre Paediatric Programme PhD studentship. N.P., L.J., O.M., I.G.F.A., L.K. and S.D.T. are supported by a European Union Horizon 2020 Marie Sk{\l}odowska–Curie Innovative Training Networks (ITN-ETN) Grant, Grant No.: 675712. N.A.P. was supported by ERASMUS+. We are grateful to AstraZeneca for providing us with AZD1208 and Inflection Biosciences for providing us with PIMi. We thank Isaia Barbieri for critical suggestions on the manuscript, BBSCR NIHR Cell phenotyping hub for flow cytometry expertise, the Bauer Core Facility at Harvard University for sequencing, and Liew Jun Mun and Stephen P. Ducray for technical assistance. Funding for the COG/ALSF Childhood Cancer Repository was provided by Alex{\textquoteright}s Lemonade Stand Foundation. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-13315-x",

language = "English",

volume = "10",

journal = "Nature Communications",

publisher = "Nature Research",

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}

Trigg, RM, Lee, LC, Prokoph, N, Jahangiri, L, Reynolds, CP, Amos Burke, GA, Probst, NA, Han, M, Matthews, JD, Kai Lim, H, Manners, E, Martinez, S, Pastor, J, Blanco-Aparicio, C, Merkel, O, de los Fayos Alonso, IG, Kodajova, P, Tangermann, S, Högler, S, Luo, J, Kenner, L & Turner, SD 2019, 'The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status', Nature Communications, vol. 10, no. 1, 5428. https://doi.org/10.1038/s41467-019-13315-x

TY - JOUR

T1 - The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status

AU - Trigg, Ricky M.

AU - Lee, Liam C.

AU - Prokoph, Nina

AU - Jahangiri, Leila

AU - Reynolds, C. Patrick

AU - Amos Burke, G. A.

AU - Probst, Nicola A.

AU - Han, Miaojun

AU - Matthews, Jamie D.

AU - Kai Lim, Hong

AU - Manners, Eleanor

AU - Martinez, Sonia

AU - Pastor, Joaquin

AU - Blanco-Aparicio, Carmen

AU - Merkel, Olaf

AU - de los Fayos Alonso, Ines Garces

AU - Kodajova, Petra

AU - Tangermann, Simone

AU - Högler, Sandra

AU - Luo, Ji

AU - Kenner, Lukas

AU - Turner, Suzanne D.

N1 - Funding Information: 4Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. 5Department of Experimental Pathology and Laboratory Animal Pathology, Institute of Clinical Pathology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna 1090, Austria. 6Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Veterinärplatz 1, Vienna 1210, Austria. 7Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA. 8Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Boltzmanngasse 20, Medical University of Vienna, Vienna 1090, Austria. 9Present address: Functional Genomics, Medicinal Science & Technology, GlaxoSmithKline, Stevenage SG1 2NY, UK. 10Present address: Amgen, Thousand Oaks, CA 91320, USA. 11Present address: OncoSec, San Diego, CA 92121, USA. 12These authors contributed equally: Ricky M. Trigg, Liam C. Lee, Nina Prokoph, Lukas Kenner, Suzanne D. Turner. *email: [email protected] Funding Information: This research is supported with funding from Children with Cancer UK (CWCUK; 16-209) awarded to S.D.T. and L.C.L., R.M.T. was supported by the CWCUK grant and L.C.L. was in receipt of a Cancer Research UK Cambridge Centre Paediatric Programme PhD studentship. N.P., L.J., O.M., I.G.F.A., L.K. and S.D.T. are supported by a European Union Horizon 2020 Marie Skłodowska–Curie Innovative Training Networks (ITN-ETN) Grant, Grant No.: 675712. N.A.P. was supported by ERASMUS+. We are grateful to AstraZeneca for providing us with AZD1208 and Inflection Biosciences for providing us with PIMi. We thank Isaia Barbieri for critical suggestions on the manuscript, BBSCR NIHR Cell phenotyping hub for flow cytometry expertise, the Bauer Core Facility at Harvard University for sequencing, and Liew Jun Mun and Stephen P. Ducray for technical assistance. Funding for the COG/ALSF Childhood Cancer Repository was provided by Alex’s Lemonade Stand Foundation. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

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U2 - 10.1038/s41467-019-13315-x

DO - 10.1038/s41467-019-13315-x

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AN - SCOPUS:85075611555

VL - 10

JO - Nature Communications

JF - Nature Communications

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M1 - 5428

ER -

The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status

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