Targeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution

Enrico Santinelli; Maria Rosaria Pascale; Zhuoer Xie; Talha Badar; Maximilian F Stahl; Jan P Bewersdorf; Carmelo Gurnari; Amer M Zeidan

doi:10.1016/j.blre.2023.101130

Targeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution

Blood Rev. 2023 Nov:62:101130. doi: 10.1016/j.blre.2023.101130. Epub 2023 Aug 29.

Authors

Enrico Santinelli¹, Maria Rosaria Pascale², Zhuoer Xie³, Talha Badar⁴, Maximilian F Stahl⁵, Jan P Bewersdorf⁶, Carmelo Gurnari⁷, Amer M Zeidan⁸

Affiliations

¹ Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, 00133 Rome, Italy; Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.
² Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, 00133 Rome, Italy.
³ Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
⁴ Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
⁵ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
⁶ Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷ Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, 00133 Rome, Italy; Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
⁸ Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA. Electronic address: amer.zeidan@yale.edu.

PMID: 37679263
DOI: 10.1016/j.blre.2023.101130

Abstract

In recent years, the therapeutic landscape of myeloid malignancies has been completely revolutionized by the introduction of several new drugs, targeting molecular alterations or pathways crucial for leukemia cells survival. Particularly, many agents targeting apoptosis have been investigated in both pre-clinical and clinical studies. For instance, venetoclax, a pro-apoptotic agent active on BCL-2 signaling, has been successfully used in the treatment of acute myeloid leukemia (AML). The impressive results achieved in this context have made the apoptotic pathway an attractive target also in other myeloid neoplasms, translating the experience of AML. Therefore, several drugs are now under investigation either as single or in combination strategies, due to their synergistic efficacy and capacity to overcome resistance. In this paper, we will review the mechanisms of apoptosis and the specific drugs currently used and under investigation for the treatment of myeloid neoplasia, identifying critical research necessities for the upcoming years.

Keywords: Apoptosis; Myeloid neoplasia; Therapeutic vulnerability; Venetoclax.

Publication types

Review

MeSH terms

Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Apoptosis
Humans
Leukemia, Myeloid, Acute* / metabolism
Myeloproliferative Disorders* / drug therapy

Substances

Antineoplastic Agents