Acute Myeloid Leukemia: Unraveling Molecular Drivers, Cellular Plasticity, and Therapeutic Vulnerabilities

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 1502

Special Issue Editor


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Guest Editor
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
Interests: acute myeloid leukemia; leukemia; hematological malignancies; clinical hematology

Special Issue Information

Dear Colleagues,

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal proliferation of undifferentiated myeloid precursors in bone marrow, leading to impaired hematopoiesis and rapid disease progression. Despite advances in molecular diagnostics and targeted therapies, AML remains associated with high morbidity and mortality, particularly in older adults and patients with adverse cytogenetic profiles.

AML is a highly heterogeneous disease, encompassing different entities, as has been recognized by the recent WHO and ICC classifications. Novel insights on the genetic complexity and molecular mechanisms of disease and on clonal evolution are required in order to identify new potential targets and disease vulnerabilities aimed at improving the efficacy of treatment, especially among high-risk entities. Furthermore, in order to better evaluate the response to treatment, developing novel biomarkers and methods for the assessment of minimal residual disease is fundamental, as currently available and validated methods are not completely satisfactory, as they are either lacking enough sensitivity or are applicable only to a minority of patients.

This Special Issue aims to present current advances in knowledge on AML, encouraging articles on AML biology, novel therapeutic strategies, and emerging biomarkers, with the ultimate scope of providing a comprehensive overview of the state-of-the-art in AML research.

Dr. Fabio Guolo
Guest Editor

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Keywords

  • acute myeloid leukemia (AML)
  • hematologic malignancy
  • AML classification
  • myeloid precursors
  • hematopoiesis
  • high-risk AML
  • biomarkers

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Published Papers (1 paper)

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Research

28 pages, 4289 KB  
Article
Synergy in Immunostimulatory and Pro-Differentiation Effects of Vitamin D Analog and Fludarabine in Acute Myeloid Leukemias
by Subhradeep Haldar, Artem Petruk, Aleksandra Marchwicka, Andrzej Kutner, Monika Biernat, Dariusz Wołowiec and Ewa Marcinkowska
Cells 2025, 14(23), 1841; https://doi.org/10.3390/cells14231841 - 21 Nov 2025
Cited by 1 | Viewed by 1172
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- [...] Read more.
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. Full article
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