Not Only a Therapeutic Target; MTOR in Hodgkin Lymphoma and Acute Lymphoblastic Leukemia

Overview

Journal Front Oncol

Specialty Oncology

Date 2024 Mar 6

PMID 38444670

Authors

Miguel Enrique Cuellar Mendoza

Francisco Raul Chavez Sanchez

Elisa Maria Dorantes Acosta

Ana Maria Niembro Zuniga

Rosana Pelayo

Marta Zapata Tarres

Affiliations

Soon will be listed here.

Abstract

Introduction: The mechanistic/mammalian target of rapamycin (mTOR) is a serine/threonine kinase, which is downregulated or upregulated and is implicated in different types of cancer including hematologic neoplasms, skin prostate, and head and neck cancer.

Aim: The aim of this study was to explore the current knowledge of mTOR signaling in acute lymphoblastic leukemia and Hodgkin lymphoma.

Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Discovery Service for National Autonomous University of Mexico, Registro Nacional de Instituciones y Empresas Científicas y Tecnológicas (RENIECYT), and Scientific Electronic Library Online (SciELO) from 1994 to 2023. A total of 269 papers were identified for acute lymphoblastic leukemia, but based on specific criteria, 15 were included; for Hodgkin lymphoma, 110 papers were identified, but 5 were included after manual searching.

Results: A total of 20 papers were evaluated, where mTOR activity is increased in patients with Hodgkin lymphoma and acute lymphoblastic leukemia by different molecular mechanisms.

Conclusions: mTOR activity is increased in patients with both hematologic neoplasms and NOTCH; interleukin 4, 7, and 9, and nuclear proteins have been studied for their role in the activation of mTOR signaling.

Citing Articles

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Stajer M, Horacek J, Kupsa T, Zak P J Appl Biomed. 2025; 22(4):165-184.

PMID: 40033805 DOI: 10.32725/jab.2024.024.

References

Martelli A, Tabellini G, Ricci F, Evangelisti C, Chiarini F, Bortul R . PI3K/AKT/mTORC1 and MEK/ERK signaling in T-cell acute lymphoblastic leukemia: new options for targeted therapy. Adv Biol Regul. 2013; 52(1):214-27. DOI: 10.1016/j.advenzreg.2011.09.019. View

Oliveira M, Akkapeddi P, Ribeiro D, Melao A, Barata J . IL-7R-mediated signaling in T-cell acute lymphoblastic leukemia: An update. Adv Biol Regul. 2018; 71:88-96. PMC: 6386770. DOI: 10.1016/j.jbior.2018.09.012. View

Hales E, Taub J, Matherly L . New insights into Notch1 regulation of the PI3K-AKT-mTOR1 signaling axis: targeted therapy of γ-secretase inhibitor resistant T-cell acute lymphoblastic leukemia. Cell Signal. 2013; 26(1):149-61. DOI: 10.1016/j.cellsig.2013.09.021. View

Cardoso B, Martins L, Santos C, Nadler L, Boussiotis V, Cardoso A . Interleukin-4 stimulates proliferation and growth of T-cell acute lymphoblastic leukemia cells by activating mTOR signaling. Leukemia. 2008; 23(1):206-8. PMC: 3099237. DOI: 10.1038/leu.2008.178. View

Wang J, Xue H, Chen Y, Xu H, Lin S, Tang X . Evaluation of Insulin-mediated Regulation of AKT Signaling in Childhood Acute Lymphoblastic Leukemia. J Pediatr Hematol Oncol. 2019; 41(2):96-104. DOI: 10.1097/MPH.0000000000001425. View

Simioni C, Martelli A, Zauli G, Melloni E, Neri L . Targeting mTOR in Acute Lymphoblastic Leukemia. Cells. 2019; 8(2). PMC: 6406494. DOI: 10.3390/cells8020190. View

Witzig T, Reeder C, LaPlant B, Gupta M, Johnston P, Micallef I . A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2010; 25(2):341-7. PMC: 3049870. DOI: 10.1038/leu.2010.226. View

Hu Y, Su H, Liu C, Wang Z, Huang L, Wang Q . DEPTOR is a direct NOTCH1 target that promotes cell proliferation and survival in T-cell leukemia. Oncogene. 2016; 36(8):1038-1047. DOI: 10.1038/onc.2016.275. View

Barata J, Keenan T, Silva A, Nadler L, Boussiotis V, Cardoso A . Common gamma chain-signaling cytokines promote proliferation of T-cell acute lymphoblastic leukemia. Haematologica. 2004; 89(12):1459-67. View

10.

Morales-Martinez M, Lichtenstein A, Vega M . Function of Deptor and its roles in hematological malignancies. Aging (Albany NY). 2021; 13(1):1528-1564. PMC: 7834987. DOI: 10.18632/aging.202462. View

11.

Huang S . mTOR Signaling in Metabolism and Cancer. Cells. 2020; 9(10). PMC: 7601420. DOI: 10.3390/cells9102278. View

12.

Johnston P, Pinter-Brown L, Warsi G, White K, Ramchandren R . Phase 2 study of everolimus for relapsed or refractory classical Hodgkin lymphoma. Exp Hematol Oncol. 2018; 7:12. PMC: 5948762. DOI: 10.1186/s40164-018-0103-z. View

13.

De J, Brown R . Tissue-microarray based immunohistochemical analysis of survival pathways in nodular sclerosing classical Hodgkin lymphoma as compared with Non-Hodgkin's lymphoma. Int J Clin Exp Med. 2010; 3(1):55-68. PMC: 2848307. View

14.

Neri L, Cani A, Martelli A, Simioni C, Junghanss C, Tabellini G . Targeting the PI3K/Akt/mTOR signaling pathway in B-precursor acute lymphoblastic leukemia and its therapeutic potential. Leukemia. 2013; 28(4):739-48. DOI: 10.1038/leu.2013.226. View

15.

Wang L, Chen B, Lin M, Cao Y, Chen Y, Chen X . Decreased expression of nucleophosmin/B23 increases drug sensitivity of adriamycin-resistant Molt-4 leukemia cells through mdr-1 regulation and Akt/mTOR signaling. Immunobiology. 2014; 220(3):331-40. DOI: 10.1016/j.imbio.2014.10.015. View

16.

Nemes K, Sebestyen A, Mark A, Hajdu M, Kenessey I, Sticz T . Mammalian target of rapamycin (mTOR) activity dependent phospho-protein expression in childhood acute lymphoblastic leukemia (ALL). PLoS One. 2013; 8(4):e59335. PMC: 3616065. DOI: 10.1371/journal.pone.0059335. View

17.

Chan K . Acute lymphoblastic leukemia. Curr Probl Pediatr Adolesc Health Care. 2002; 32(2):40-9. DOI: 10.1067/mps.2002.121790. View

18.

Mark A, Hajdu M, Varadi Z, Sticz T, Nagy N, Csomor J . Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease--a combined tissue microarray, in vitro and in vivo study. BMC Cancer. 2013; 13:250. PMC: 3665449. DOI: 10.1186/1471-2407-13-250. View

19.

Wang Y, Bi Y, Chen X, Li C, Li Y, Zhang Z . Histone Deacetylase SIRT1 Negatively Regulates the Differentiation of Interleukin-9-Producing CD4(+) T Cells. Immunity. 2016; 44(6):1337-49. DOI: 10.1016/j.immuni.2016.05.009. View

20.

Larson Gedman A, Chen Q, Kugel Desmoulin S, Ge Y, LaFiura K, Haska C . The impact of NOTCH1, FBW7 and PTEN mutations on prognosis and downstream signaling in pediatric T-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Leukemia. 2009; 23(8):1417-25. PMC: 2726275. DOI: 10.1038/leu.2009.64. View