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Cells
Volume 14
Issue 23
10.3390/cells14231841
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Synergy in Immunostimulatory and Pro-Differentiation Effects of Vitamin D Analog and Fludarabine in Acute Myeloid Leukemias

by
Subhradeep Haldar
1,
Artem Petruk
1,
Aleksandra Marchwicka
1,
Andrzej Kutner
2,
Monika Biernat
3,
Dariusz Wołowiec
3 and
Ewa Marcinkowska
1,*
1
Department of Medical Biotechnology, Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland
2
Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland
3
Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław Medical University, Pasteura 4, 50-367 Wrocław, Poland
*
Author to whom correspondence should be addressed.
Cells 2025, 14(23), 1841; https://doi.org/10.3390/cells14231841
Submission received: 2 October 2025 / Revised: 14 November 2025 / Accepted: 19 November 2025 / Published: 21 November 2025
(This article belongs to the Special Issue Acute Myeloid Leukemia: Unraveling Molecular Drivers, Cellular Plasticity, and Therapeutic Vulnerabilities)
Versions Notes

Abstract

Acute myeloid leukemia (AML) is an aggressive and often fatal hematopoietic malignancy, diagnosed predominantly in the elderly. The five-year survival of patients with AML is as low as 30%. Differentiation therapy of a subtype of AML, named acute promyelocytic leukemia (APL), using all-trans retinoic acid (ATRA) was the most successful example of a targeted therapy against AML. Epigenetic-based differentiation therapies for other subtypes of AML are also showing improvements in response and in survival rates. Thus, in this study, we investigated a potential differentiation therapy with a combination of 1,25-dihydroxyvitamin D (1,25D) analog (named PRI5202) and low concentration of Fludarabine. We show that such a combination elicits immunostimulatory and pro-differentiation effects in AML cells, specifically in those with activating mutations in fibroblast growth factor receptor (FGFR) and Janus kinase (JAK) pathways. We show here that both PRI5202 and Fludarabine are potent activators of the transcription of many innate immunity-related genes, and that, in combination, their effects are in many aspects synergistic. We propose that such a low-intensity regimen may be suitable for older patients with AML, who are unfit for intensive chemotherapy. We also present data indicating that PRI5202 induces myeloid differentiation in blasts from patients with myelodysplastic syndrome (MDS), and we propose to further investigate PRI5202 as a differentiation therapy for patients suffering from MDS.
Keywords: acute myeloid leukemia; differentiation; immune stimulation; 1,25-dihydroxyvitamin D analog; fludarabine acute myeloid leukemia; differentiation; immune stimulation; 1,25-dihydroxyvitamin D analog; fludarabine

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MDPI and ACS Style

Haldar, S.; Petruk, A.; Marchwicka, A.; Kutner, A.; Biernat, M.; Wołowiec, D.; Marcinkowska, E. Synergy in Immunostimulatory and Pro-Differentiation Effects of Vitamin D Analog and Fludarabine in Acute Myeloid Leukemias. Cells 2025, 14, 1841. https://doi.org/10.3390/cells14231841

AMA Style

Haldar S, Petruk A, Marchwicka A, Kutner A, Biernat M, Wołowiec D, Marcinkowska E. Synergy in Immunostimulatory and Pro-Differentiation Effects of Vitamin D Analog and Fludarabine in Acute Myeloid Leukemias. Cells. 2025; 14(23):1841. https://doi.org/10.3390/cells14231841

Chicago/Turabian Style

Haldar, Subhradeep, Artem Petruk, Aleksandra Marchwicka, Andrzej Kutner, Monika Biernat, Dariusz Wołowiec, and Ewa Marcinkowska. 2025. "Synergy in Immunostimulatory and Pro-Differentiation Effects of Vitamin D Analog and Fludarabine in Acute Myeloid Leukemias" Cells 14, no. 23: 1841. https://doi.org/10.3390/cells14231841

APA Style

Haldar, S., Petruk, A., Marchwicka, A., Kutner, A., Biernat, M., Wołowiec, D., & Marcinkowska, E. (2025). Synergy in Immunostimulatory and Pro-Differentiation Effects of Vitamin D Analog and Fludarabine in Acute Myeloid Leukemias. Cells, 14(23), 1841. https://doi.org/10.3390/cells14231841

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