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Acute Myeloid Leukemia: Current Progress and Future Directions
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Acute Myeloid Leukemia: Current Progress and Future Directions

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Personalized Therapy in Clinical Medicine".

Deadline for manuscript submissions: 15 October 2026 | Viewed by 4915

Special Issue Editors

Dr. Valeria Visconte

E-Mail Website
Guest Editor
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA
Interests: myeloid malignancies; bone marrow failure syndromes; RNA splicing
Special Issues, Collections and Topics in MDPI journals
Dr. Luca Guarnera

E-Mail Website
Guest Editor
Hematology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy
Interests: acute myeloid leukemia; myelodysplastic syndromes; myeloproliferative neoplasms; acute promyelocytic leukemia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acute myeloid leukemia (AML) is an aggressive malignancy spanning heterogenous clinical and molecular phenotypes. In recent years, huge advances in our understanding of the disease’s biology have led us to gain deeper insight into the genetic features and the bone marrow microenvironment changes underpinning the process of leukemogenesis, paving the way to targeted treatments. Therefore, paired with these findings, there has been a rise in attention toward support therapies and careful assessments of patients’ wellbeing. All in all, these novelties have manifested in the investigation and successful introduction of target therapies in clinical practice; more precise risk stratification; and AML management tailored to both the disease’s biological features and patients’ characteristics. Thus, this Special Issue will focus on the recent advances concerning all facets of personalized AML management, including both treatment investigations and translational research, as well as the bench-side management of complications and all-day practice. Moreover, current and future risk disease stratifications, prognostic markers and models, and applications of novel techniques regarding the disease’s multimodal nature will be considered. We will highly appreciate and welcome the submissions of original papers and reviews in line with the aim of this Special Issue.

Dr. Valeria Visconte
Dr. Luca Guarnera
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (3 papers)

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Research

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15 pages, 712 KB  
Article
Personalized Venetoclax Dose Adjustment in Unfit Acute Myeloid Leukemia Patients: A Real-Life Case Series Study
by Serena Luponio, Bianca Serio, Idalucia Ferrara, Andrea Gigantiello, Anna Maria Della Corte, Denise Morini, Italia Conversano, Francesco Verdesca, Francesca Velino, Anna Maria Sessa, Simona Caruso, Rossella Marcucci, Martina De Leucio, Valentina Giudice, Maddalena Langella and Carmine Selleri
J. Pers. Med. 2026, 16(4), 200; https://doi.org/10.3390/jpm16040200 - 2 Apr 2026
Viewed by 446
Abstract
Background/Objectives: Minimal residual disease (MRD) negativity is associated with improved outcomes in acute myeloid leukemia (AML) patients. In this retrospective observational real-life case series study, we investigated the efficacy and safety of venetoclax dose adjustment in unfit AML patients and the role [...] Read more.
Background/Objectives: Minimal residual disease (MRD) negativity is associated with improved outcomes in acute myeloid leukemia (AML) patients. In this retrospective observational real-life case series study, we investigated the efficacy and safety of venetoclax dose adjustment in unfit AML patients and the role of WT1 expression levels as a surrogate marker of MRD monitoring. Methods: A total of 24 consecutive unfit AML patients treated with azacytidine and venetoclax were enrolled in this study, and MRD monitoring was performed by flow cytometry as per international guidelines and by WT1 expression levels assessed by RT-qPCR. Dose adjustment of venetoclax was decided based on MRD status and the onset of grade > 2 neutropenia. Results: The overall response rate was 87.5%, and 16 patients achieved a response already at the first re-evaluation (66.7%). No statistically significant differences were observed between patients who received the standard dose and those with venetoclax dose adjustment in terms of overall survival (19.6 months vs. 30.1 months, respectively; p = 0.9428) and progression-free survival (not reached vs. 22.1 months, respectively; p = 0.3865), although a numerical trend toward lower relapse rates was observed in subjects with late (33.3%) or early and late dose reduction (37.5%) compared to those who had dose adjustment only at the first re-evaluation (75%) (p = 0.3014). The toxicity rate was 33.3% in patients who had early and late dose adjustments, which was lower than that observed with early adjustment (58.3%) and than that reported in the VIALE-A study (84%). Conclusions: Reduced-dose venetoclax regimens (from 28 to 21 days per cycle) in unfit AML patients do not affect response rates or survival and are associated with comparable rates of neutropenia and infectious events, supporting flexible dosing strategies based on patient response and side effects. In addition, WT1 expression could serve as a reliable marker for MRD monitoring. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia: Current Progress and Future Directions)
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19 pages, 5889 KB  
Article
Immunophenotypic Heterogeneity and Clonal Sweep in Acute Myeloid Leukemia Revealed by Flow Cytometry: A Case Series Study
by Angela Bertolini, Marisa Gorrese, Serena Luponio, Francesca Picone, Annapaola Campana, Francesco Verdesca, Francesca Velino, Anna Maria Sessa, Simona Caruso, Martina De Leucio, Rossella Marcucci, Anna Maria Della Corte, Pasqualina Scala, Maddalena Langella, Bianca Serio, Carmine Selleri and Valentina Giudice
J. Pers. Med. 2026, 16(4), 180; https://doi.org/10.3390/jpm16040180 - 25 Mar 2026
Viewed by 548
Abstract
Background/Objectives: Clonal evolution is mainly defined based on the appearance or expansion of clones harboring specific somatic mutations and/or cytogenetic abnormalities, whereas few studies have investigated immunophenotypic heterogeneity assessed by flow cytometry and its relationship with disease progression. In this study, flow [...] Read more.
Background/Objectives: Clonal evolution is mainly defined based on the appearance or expansion of clones harboring specific somatic mutations and/or cytogenetic abnormalities, whereas few studies have investigated immunophenotypic heterogeneity assessed by flow cytometry and its relationship with disease progression. In this study, flow cytometry immunophenotyping of acute myeloid leukemia (AML) was carried out to identify phenotypic subclones based on antigen expression and to investigate clonal sweep. Methods: A total of 24 patients diagnosed with AML followed at the Hematology and Transplant Center of Salerno were included. Bone marrow or peripheral blood specimens were subjected to flow cytometry immunophenotyping and leukemic cell characterization. Phenotypic profiles were also compared to molecular alterations detected by next-generation sequencing. Results: We found that flow cytometry-defined clonal heterogeneity was more complex than molecular heterogeneity at diagnosis and disease relapse. Flow cytometry enabled the identification of small phenotypic subclones that were not detected by molecular profiling and that, in several cases, expanded over time, consistent with a phenotypic clonal sweep. The presence of small clones was associated with shorter progression-free survival and overall survival. Conclusions: Flow cytometric clonal heterogeneity, especially the presence of small clones (defined by antigen expression from 2 to 30%), may serve as an additional prognostic factor in AML. Immunophenotyping integrated with molecular data may improve risk stratification, enhance measurable residual disease assessment, and contribute to a more personalized disease monitoring strategy. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia: Current Progress and Future Directions)
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Review

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27 pages, 2698 KB  
Review
Metabolic Signature of FLT3-Mutated AML: Clinical and Therapeutic Implications
by Cristina Banella, Gianfranco Catalano, Maura Calvani, Eleonora Candi, Nelida Ines Noguera and Serena Travaglini
J. Pers. Med. 2025, 15(9), 431; https://doi.org/10.3390/jpm15090431 - 8 Sep 2025
Cited by 2 | Viewed by 2692
Abstract
Acute Myeloid Leukemia (AML) is a genetically and clinically heterogeneous malignancy marked by poor prognosis and limited therapeutic options, especially in older patients. While conventional treatments such as the “7 + 3” chemotherapy regimen and allogeneic stem cell transplantation remain standard care options, [...] Read more.
Acute Myeloid Leukemia (AML) is a genetically and clinically heterogeneous malignancy marked by poor prognosis and limited therapeutic options, especially in older patients. While conventional treatments such as the “7 + 3” chemotherapy regimen and allogeneic stem cell transplantation remain standard care options, the advent of next-generation sequencing (NGS) has transformed our understanding of AML’s molecular complexity. Among the emerging hallmarks of AML, metabolic reprogramming has gained increasing attention for its role in supporting leukemic cell proliferation, survival, and therapy resistance. Distinct AML subtypes—shaped by specific genetic alterations, including FLT3, NPM1, and IDH mutations—exhibit unique metabolic phenotypes that reflect their underlying molecular landscapes. Notably, FLT3-ITD mutations are associated with enhanced reactive oxygen species (ROS) production and altered energy metabolism, contributing to disease aggressiveness and poor clinical outcomes. This review highlights the interplay between metabolic plasticity and genetic heterogeneity in AML, with a particular focus on FLT3-driven metabolic rewiring. We discuss recent insights into how these metabolic dependencies may be exploited therapeutically, offering a rationale for the development of metabolism-targeted strategies in the treatment of FLT3-mutated AML. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia: Current Progress and Future Directions)
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