Page 300 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
agents and delayed leukemia expansion in vivo, with no detectable toxicity identified in the peripheral blood (On- line Supplementary Figure S2K). Leucettinib-21 has recently completed regulatory preclinical safety studies and is primed for early phase clinical assessment. Strikingly, studies have demonstrated the preclinical impact of targeting DYRK1A activity in different subtypes of childhood leukemia,8 further emphasizing the potential benefit for investigating Leucet- tinib-21 or other new potent DYRK1A inhibitors in clinical trials for ALL.
Altogether, this study has established and comprehensively characterized the first DS-ALL cell lines, providing suit- able and clinically relevant cellular models to identify new molecular weaknesses in DS-ALL and test the efficacy of novel targeted therapies (as exemplified here with DYRK1A inhibition), alone or in combination with standard of care, to ultimately develop new, less toxic treatments to improve the outcome for children with DS-ALL.
Authors
Shannon L. Carey-Smith,1,2* Maryam H. Simad,1* Kunjal Panchal,1,2 Carlos Aya-Bonilla,1 Hannah Smolders,1 Sang Lin,1 Jesse D. Armitage,1 Vivien T. Nguyen,1 Kathryn Bentley,1 Jette Ford,1 Sajla Singh,1 Joyce Oommen,1 Anouchka P. Laurent,3 Thomas Mercher,3 John D. Crispino,4 Andrew P. Montgomery,5 Michael Kassiou,5 Thierry Besson,6 Emmanuel Deau,7 Laurent Meijer,7 Laurence C. Cheung,1,2,8 Rishi S. Kotecha1,2,9,10 and Sébastien Malinge1,2,10
1Telethon Kids Cancer Center, Telethon Kids Institute, Perth, Western Australia, Australia; 2Curtin Medical School, Curtin University, Perth, Western Australia, Australia; 3U1170 INSERM, Gustave Roussy, Villejuif, France; 4Department of Hematology, St Jude Children’s Hospital, Memphis, TN, USA; 5School of Chemistry, University of Sydney, New South Wales, Australia; 6University Rouen Normandie, INSA Rouen Normandie, CNRS, COBRA UMR 6014, Rouen, France; 7Perha Pharmaceuticals, Perharidy Peninsula, Roscoff, France; 8Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia; 9Department of Clinical Hematology, Oncology, Blood and Marrow Transplantation, Perth Children’s Hospital, Perth, Western Australia, Australia and 10University of Western Australia, Perth, Western Australia, Australia
*SLC-S and MHS contributed equally as first authors.
Correspondence:
S. MALINGE - sebastien.malinge@telethonkids.org.au
https://doi.org/10.3324/haematol.2023.284271
Received: September 13, 2023. Accepted: February 19, 2024. Early view: February 29, 2024.
©2024 Ferrata Storti Foundation Published under a CC BY-NC license
Disclosures
JDC is a member of the scientific advisory board for Alethiomics, a consultant for Cellarity, and receives research funding from Syndax. LM is a founder of Perha Pharmaceuticals. ED and LM are co- inventors in the Leucettinib patents. RSK discloses advisory board participation from Jazz Pharmaceuticals, Amgen and Link Healthcare. All other authors have no conflicts of interest to disclose.
Contributions
SLCS, MHS and SM conceived and designed the experiments. SLCS, MHS, KP, CAB, HS, SL, JDA, VTN, KB, JF, SS, JO and SM performed the experiments. APL, TM, JDC, TB, APM, MK, ED and LM provided reagents, materials and technical insight. SLCS, MHS, KP, CAB, LCC and RSK significantly contributed to analysis and interpretation of the results. SM supervised the project. SLCS and SM wrote the manuscript. All authors edited and approved the final version of the manuscript for submission.
Acknowledgments
We thank L. Munoz, T. Johns, G. Chua, P. Kumar, T. Lassmann, and staff members of the Bioresources facility at Telethon Kids Institute for their support in obtaining reagents, processing samples and housing/monitoring animals related to this study.
Funding
This research was supported by Australian Government Research Training Program (RTP) Scholarships (to SLCS and KP). CAB is supported by a Fellowship from the Jerome Lejeune and Sisley- d’Ornano Foundations. TB is supported by the University of Rouen Normandy, INSA Rouen Normandy, the Centre National de la Recherche Scientifique (CNRS), European Regional Development Fund (ERDF), Labex SynOrg (ANR-11-LABX-0029), Carnot Institute I2C, the XL-Chem Graduate School of Research (ANR-18-EURE-0020 XL CHEM), and by Region Normandie. APM is supported by a postdoctoral research fellowship from the University of Sydney’s
Drug Discovery Initiative. MK is a recipient of a National Health and Medical Research Council Principal Research Fellowship (APP1154692). LM is supported by grants from the Jerome Lejeune Foundation, l’Agence Nationale de la Recherche (ANR) (DYRK-DOWN), BpiFrance (i-Nov, vague 9), the European Union’s Horizon 2020 research and innovation programme (Grant #848077) (GO-DS21), and the European Innovation Council (EIC) Accelerator Down-Autonomy project (190138295). SM is supported by a fellowship from the Cancer Council Western Australia (CCWA, Grant #877). This study was supported by project grants from the Child Cancer Research Foundation (RSK, LCC and SM), Cancer Council Western Australia (Grant #1068) and the Jerome Lejeune Foundation (Grant #1806).
Data-sharing statement
RNA-sequencing files are available via the Gene Expression Omnibus (GEO) database under the accession number GSE245056.
Haematologica | 109 July 2024
2314