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NOTCH1 and the pathobiology of ALK-positive ALCL
tant cell lines remain sensitive to NOTCH1 inhibition. Hence, inhibition of NOTCH1 via GSI might represent a therapeutic option for both treatment-naïve and ALK inhibitor-resistant ALCL – while NOTCH1 expression may be a viable biomarker predictive of relapse.
Disclosures
No conflicts of interest to disclose.
Contributions
HL: conceptualization, methodology, investigations, writing of the original draft, and visualization. NP: conceptualization, investigations, writing, review and editing. JDM: software, visualization, formal analysis, writing, review and editing. MS, SH, EN, MFM, AE, MC, LM, CGP, GH, CL, SP, AJ, AF, AM, OW, GI, LL, OM, WK, SM, IA, MW, GAAB and LK: resources. AFA: investigations, software. SPD: investigation, writing, review and editing. WW and CDW: resources, writing, review and editing. MZ: software and formal analysis. TLB: conceptualization, methodology, software, writing, review and editing. SDT: conceptualization, resources, writing, review, editing, supervision, project administration, and acquisition of funding.
Acknowledgments
The authors would like to thank Professor Christopher Aster
and Dr Johnson (Harvard Medical School) for providing the full- length NOTCH1 cDNA. We also thank: the Cambridge NIHR BRC Cell Phenotyping Hub; Medical Research Laboratories Core for Sanger sequencing; Washington State University Genomic Sequencing for library preparation, quality control and sequencing; the CCLG Tissue Bank, the CCLG centers and the ECMC Pediatric Network for the collection and provision of tis- sue samples. We especially thank the patients and families who voluntarily donated the samples.
Funding
This work was supported by grants from the Ministry of Science, Kingdom of Saudi Arabia to SDT, AI and SM (grant number 74497) and Bloodwise to SDT (grant number 12065). HL is supported by a Department of Pathology, University of Cambridge Pathology Centenary Fund PhD studentship. SDT, LK, OM, SK, NP, SPD, CGP, WW, CDW and CL are recipients of funds from a European Union Horizon 2020 Marie Sklodowska-Curie Innovative Training Network (ITN- ETN) grant, award n. 675712. CL is supported by a Czech Science Foundation research grant n. 19-23424Y and by research infrastructures EATRIS-CZ (LM2015064) and the NCMG (LM2015091) funded by MEYS CR. WK is support- ed by the KinderkrebsInitiative Buchholz, Holm-Seppensen. The CCLG Tissue Bank is funded by Cancer Research UK and CCLG.
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