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Cutting Edge Molecular Therapy for Acute Myeloid Leukemia
Open AccessArticle

A Screening of Antineoplastic Drugs for Acute Myeloid Leukemia Reveals Contrasting Immunogenic Effects of Etoposide and Fludarabine

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Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia “Seràgnoli”, Università degli Studi, 40138 Bologna, Italy
2
Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, 40138 Bologna, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6802; https://doi.org/10.3390/ijms21186802
Received: 8 September 2020 / Accepted: 15 September 2020 / Published: 16 September 2020
(This article belongs to the Special Issue Genetics, Biology, and Treatment of Acute Myeloid Leukemia 2.0)
Background: Recent evidence demonstrated that the treatment of acute myeloid leukemia (AML) cells with daunorubicin (DNR) but not cytarabine (Ara-C) results in immunogenic cell death (ICD). In the clinical setting, chemotherapy including anthracyclines and Ara-C remains a gold standard for AML treatment. In the last decade, etoposide (Eto) and fludarabine (Flu) have been added to the standard treatment for AML to potentiate its therapeutic effect and have been tested in many trials. Very little data are available about the ability of these drugs to induce ICD. Methods: AML cells were treated with all four drugs. Calreticulin and heat shock protein 70/90 translocation, non-histone chromatin-binding protein high mobility group box 1 and adenosine triphosphate release were evaluated. The treated cells were pulsed into dendritic cells (DCs) and used for in vitro immunological tests. Results: Flu and Ara-C had no capacity to induce ICD-related events. Interestingly, Eto was comparable to DNR in inducing all ICD events, resulting in DC maturation. Moreover, Flu was significantly more potent in inducing suppressive T regulatory cells compared to other drugs. Conclusions: Our results indicate a novel and until now poorly investigated feature of antineoplastic drugs commonly used for AML treatment, based on their different immunogenic potential. View Full-Text
Keywords: acute myeloid leukemia; immunogenic cell death; chemotherapy; fludarabine; etoposide acute myeloid leukemia; immunogenic cell death; chemotherapy; fludarabine; etoposide
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Ocadlikova, D.; Iannarone, C.; Redavid, A.R.; Cavo, M.; Curti, A. A Screening of Antineoplastic Drugs for Acute Myeloid Leukemia Reveals Contrasting Immunogenic Effects of Etoposide and Fludarabine. Int. J. Mol. Sci. 2020, 21, 6802.

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