Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia

Sergio, Ilaria; Varricchio, Claudia; Squillante, Federica; Cantale Aeo, Noemi Martina; Campese, Antonio Francesco; Felli, Maria Pia

doi:10.3390/ijms252312839

Open AccessReview

Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia

by

Ilaria Sergio

^1,†

,

Claudia Varricchio

^2,†,

Federica Squillante

¹,

Noemi Martina Cantale Aeo

²,

Antonio Francesco Campese

^2,‡ and

Maria Pia Felli

^1,*,‡

¹

Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy

²

Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors also contributed equally to this work.

Int. J. Mol. Sci. 2024, 25(23), 12839; https://doi.org/10.3390/ijms252312839

Submission received: 18 October 2024 / Revised: 24 November 2024 / Accepted: 26 November 2024 / Published: 29 November 2024

(This article belongs to the Special Issue Molecular Aspects of Hematological Malignancies and Benign Hematological Disorders—3rd Edition)

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Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with poor response to conventional therapy, derived from hematopoietic progenitors committed to T-cell lineage. Relapsed/Refractory patients account for nearly 20% of childhood and 45% of adult cases. Aberrant Notch signaling plays a critical role in T-ALL pathogenesis and therapy resistance. Notch inhibition is a promising therapeutic target for personalized medicine, and a variety of strategies to prevent Notch activation, including γ-secretase (GS) inhibitors (GSIs) and antibodies neutralizing Notch receptors or ligands, have been developed. Disruption of apoptosis is pivotal in cancer development and progression. Different reports evidenced the interplay between Notch and the anti-apoptotic Bcl-2 family proteins in T-ALL. Although based on early research data, this review discusses recent advances in directly targeting Notch receptors and the use of validated BH3 mimetics for the treatment of T-ALL and their combined action in light of current evidence of their use.

Keywords: Notch; Bcl-2 family proteins; T-cell leukemia; BH3 mimetics; Notch inhibitors

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MDPI and ACS Style

Sergio, I.; Varricchio, C.; Squillante, F.; Cantale Aeo, N.M.; Campese, A.F.; Felli, M.P. Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia. Int. J. Mol. Sci. 2024, 25, 12839. https://doi.org/10.3390/ijms252312839

AMA Style

Sergio I, Varricchio C, Squillante F, Cantale Aeo NM, Campese AF, Felli MP. Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia. International Journal of Molecular Sciences. 2024; 25(23):12839. https://doi.org/10.3390/ijms252312839

Chicago/Turabian Style

Sergio, Ilaria, Claudia Varricchio, Federica Squillante, Noemi Martina Cantale Aeo, Antonio Francesco Campese, and Maria Pia Felli. 2024. "Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia" International Journal of Molecular Sciences 25, no. 23: 12839. https://doi.org/10.3390/ijms252312839

APA Style

Sergio, I., Varricchio, C., Squillante, F., Cantale Aeo, N. M., Campese, A. F., & Felli, M. P. (2024). Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia. International Journal of Molecular Sciences, 25(23), 12839. https://doi.org/10.3390/ijms252312839

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia

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