Page 306 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
666-15. Cytotoxicity was observed at drug concentrations, which reduced tumor growth without overt toxicity in mice models, suggesting a potential therapeutic window of CREB inhibition.8,9 Together, these data suggest that MRD-directed therapies should be cell-cycle independent and that the CREB pathway is a valid therapeutic target for both T- and B-lineage ALL cells.
Authors
Dino Masic,1 Hayden L Bell,1 Frederik W van Delft,1,2 and Julie Anne Elizabeth Irving1
1Wolfson Childhood Cancer Research Center, Newcastle University Center for Cancer and 2Department of Pediatric Hematology and Oncology, Great North Children’s Hospital, Newcastle upon Tyne, UK
Correspondence:
J. IRVING - Julie.Irving@newcastle.ac.uk
https://doi.org/10.3324/haematol.2023.284335
Received: September 26, 2023. Accepted: February 14, 2024. Early view: February 22, 2024.
References
1. Masic D, Fee K, Bell H, et al. Hyperactive CREB subpopulations increase during therapy in pediatric B-lineage acute lymphoblastic leukemia. Haematologica. 2023;108(4):981-992.
2. Gocho Y, Liu J, Hu J, et al. Network-based systems pharmacology reveals heterogeneity in LCK and BCL2 signaling and therapeutic sensitivity of T-cell acute lymphoblastic leukemia. Nat Cancer. 2021;2(3):284-299.
3. Shi Y, Beckett MC, Blair HJ, et al. Phase II-like murine trial identifies synergy between dexamethasone and dasatinib in T-cell acute lymphoblastic leukemia. Haematologica. 2021;106(4):1056-1066.
4. Recasens A, Munoz L. Targeting cancer cell dormancy. Trends Pharmacol Sci. 2019;40(2):128-141.
5. Ebinger S, Ozdemir EZ, Ziegenhain C, et al. Characterization of rare, dormant, and therapy-resistant cells in acute lymphoblastic leukemia. Cancer Cell. 2016;30(6):849-862.
6. Sapio L, Salzillo A, Ragone A, Illiano M, Spina A, Naviglio S.
©2024 Ferrata Storti Foundation Published under a CC BY license
Disclosures
JAEI has received funding from Hoffmann-La Roche Ltd for work unrelated to this manuscript. All other authors have no conflicts of interest to disclose.
Contributions
DM and HLB performed research. JAEI, DM and HLB designed the research study. DM, JAEI, HLB and FWvD analyzed the data. DM and JAEI wrote the first draft of the paper and all authors critically reviewed and approved the final draft.
Acknowledgments
The authors are indebted to Andy Filby and David McDonald from the Newcastle Flow Facility for their expertise in mass cytometric analyses.
Funding
The authors would like to gratefully acknowledge Children with Cancer UK, Newcastle Hospitals NHS Foundation Trust and JGW Paterson for funding this study.
Data-sharing statement
Data is available on request.
Targeting CREB in cancer therapy: a key candidate or one of
many? An update. Cancers. 2020;12(11):3166.
7. van der Sligte NE, Kampen KR, ter Elst A, et al. Essential role
for cyclic-AMP responsive element binding protein 1 (CREB) in the survival of acute lymphoblastic leukemia. Oncotarget. 2015;6(17):14970-14981.
8. Xie F, Li BX, Kassenbrock A, et al. Identification of a potent inhibitor of CREB-mediated gene transcription with efficacious in vivo anticancer activity. J Med Chem. 2015;58(12):5075-5087.
9. Li BBX, Gardner R, Xue CH, et al. Systemic Inhibition of CREB is Well-tolerated in vivo. Sci Rep. 2016;6:34513.
10. Irving J, Jesson J, Virgo P, et al. Establishment and validation of a standard protocol for the detection of minimal residual disease in B lineage childhood acute lymphoblastic leukemia by flow cytometry in a multi-center setting. Haematologica. 2009;94(6):870-874.
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