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Biomedicines
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Molecular Research on Acute Myeloid Leukemia (AML) Volume II
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Molecular Research on Acute Myeloid Leukemia (AML) Volume II

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 3817

Special Issue Editor

Dr. Michele Gottardi

E-Mail Website
Guest Editor
Onco Hematology, Department of Oncology, Veneto Institute of Oncology IOV, IRCCS, 31033 Padua, Italy
Interests: AML; core binding factor AML; novel agents; bone marrow microenviroment; HSCT
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acute myeloid leukemia (AML) is an extremely heterogeneous disease that originates from an aberrant proliferation and/or block in the normal differentiation of hematopoietic cells. Remarkable advances have been made during the last decade to understand the AML genome, both at disease diagnosis and relapse and to explain how genetic alterations might influence the distinct biological subgroups and their role in clonal evolution. The development of novel innovative technologies has not only allowed us to detect the genetic alterations as early as possible, but also to understand the molecular pathogenesis of AML, ultimately opening the door to personalized therapy for specific AML patient populations, with promising results. Finally, understanding the metabolic consequences of specific driver genetic lesions sounds particularly attractive for identifying future metabolic-targeted therapies with the aim of overcoming AML refractoriness. In the present Special Issue, we invite authors to submit original research papers and reviews on how deciphering the molecular mechanisms underlying the pathogenesis of the disease could change our current diagnostic and therapeutic approach in treating AML.

Dr. Michele Gottardi
Guest Editor

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 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomedicines 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.

Keywords

  • acute myeloid leukemia
  • molecular pathogenesis
  • novel AML therapies
  • AML clonal evolution
  • epigenetic alterations
  • multi-omics
  • precision medicine
  • leukemia stem cell

Published Papers (4 papers)

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Research

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11 pages, 1153 KiB  
Article
Blast-Derived Small Extracellular Vesicles in the Plasma of Patients with Acute Myeloid Leukemia Predict Responses to Chemotherapy
by Michael Boyiadzis, Chang-Sook Hong, Saigopalakrishna Yerneni, Annie Im, Brenda Diergaarde and Theresa L. Whiteside
Biomedicines 2023, 11(12), 3236; https://doi.org/10.3390/biomedicines11123236 - 7 Dec 2023
Viewed by 995
Abstract
The small extracellular vesicles (sEV) accumulating in acute myeloid leukemia (AML) patients’ plasma are mixtures of vesicles produced by leukemic and non-malignant cells. sEV originating from leukemia blasts could serve as potential non-invasive biomarkers of AML response to therapy. To isolate blast-derived sEV [...] Read more.
The small extracellular vesicles (sEV) accumulating in acute myeloid leukemia (AML) patients’ plasma are mixtures of vesicles produced by leukemic and non-malignant cells. sEV originating from leukemia blasts could serve as potential non-invasive biomarkers of AML response to therapy. To isolate blast-derived sEV from patients’ plasma, we developed a bioprinted microarray-based immunoassay using monoclonal antibodies (mAbs) specific for leukemia-associated antigens (LAAs) and mAbs specific for a mix of tetraspanins (CD9, CD63, and CD81). We determined the proportion of LAA+ sEV relative to total plasma sEV (the LAA+/total sEV ratio) in serially collected samples of newly diagnosed AML patients prior to, during, and after chemotherapy. At AML diagnosis, the LAA+/total sEV ratio was significantly higher in patients than in healthy donors (HDs). In patients who achieved complete remission (CR) after induction chemotherapy, the LAA+/total sEV ratios significantly decreased after each chemotherapy cycle to levels seen in HDs. In contrast, the LAA+/total sEV ratios in AML patients with persistent leukemia after therapy remained elevated during and after therapy, as did the percentage of leukemic blasts in these patients’ bone marrows. The LAA+/total sEV ratio emerges as a promising non-invasive biomarker of leukemia response to therapy. Full article
(This article belongs to the Special Issue Molecular Research on Acute Myeloid Leukemia (AML) Volume II)
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Review

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18 pages, 1447 KiB  
Review
Therapy-Related Myeloid Neoplasm: Biology and Mechanistic Aspects of Malignant Progression
by Serena Travaglini, Massimiliano Marinoni, Valeria Visconte and Luca Guarnera
Biomedicines 2024, 12(5), 1054; https://doi.org/10.3390/biomedicines12051054 - 10 May 2024
Viewed by 377
Abstract
Therapy-related myeloid neoplasms (t-MN) arise after a documented history of chemo/radiotherapy as treatment for an unrelated condition and account for 10–20% of myelodysplastic syndromes and acute myeloid leukemia. T-MN are characterized by a specific genetic signature, aggressive features and dismal prognosis. The nomenclature [...] Read more.
Therapy-related myeloid neoplasms (t-MN) arise after a documented history of chemo/radiotherapy as treatment for an unrelated condition and account for 10–20% of myelodysplastic syndromes and acute myeloid leukemia. T-MN are characterized by a specific genetic signature, aggressive features and dismal prognosis. The nomenclature and the subsets of these conditions have changed frequently over time, and despite the fact that, in the last classification, they lost their autonomous entity status and became disease qualifiers, the recognition of this feature remains of major importance. Furthermore, in recent years, extensive studies focusing on clonal hematopoiesis and germline variants shed light on the mechanisms of positive pressure underpinning the rise of driver gene mutations in t-MN. In this manuscript, we aim to review the evolution of defining criteria and characteristics of t-MN from a clinical and biological perspective, the advances in mechanistic aspects of malignant progression and the challenges in prevention and management. Full article
(This article belongs to the Special Issue Molecular Research on Acute Myeloid Leukemia (AML) Volume II)
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26 pages, 648 KiB  
Review
Transplant Eligible and Ineligible Elderly Patients with AML—A Genomic Approach and Next Generation Questions
by Paul Sackstein, Alexis Williams, Rachel Zemel, Jennifer A. Marks, Anne S. Renteria and Gustavo Rivero
Biomedicines 2024, 12(5), 975; https://doi.org/10.3390/biomedicines12050975 - 29 Apr 2024
Viewed by 513
Abstract
The management of elderly patients diagnosed with acute myelogenous leukemia (AML) is complicated by high relapse risk and comorbidities that often preclude access to allogeneic hematopoietic cellular transplantation (allo-HCT). In recent years, fast-paced FDA drug approval has reshaped the therapeutic landscape, with modest, [...] Read more.
The management of elderly patients diagnosed with acute myelogenous leukemia (AML) is complicated by high relapse risk and comorbidities that often preclude access to allogeneic hematopoietic cellular transplantation (allo-HCT). In recent years, fast-paced FDA drug approval has reshaped the therapeutic landscape, with modest, albeit promising improvement in survival. Still, AML outcomes in elderly patients remain unacceptably unfavorable highlighting the need for better understanding of disease biology and tailored strategies. In this review, we discuss recent modifications suggested by European Leukemia Network 2022 (ELN-2022) risk stratification and review recent aging cell biology advances with the discussion of four AML cases. While an older age, >60 years, does not constitute an absolute contraindication for allo-HCT, the careful patient selection based on a detailed and multidisciplinary risk stratification cannot be overemphasized. Full article
(This article belongs to the Special Issue Molecular Research on Acute Myeloid Leukemia (AML) Volume II)
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Other

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11 pages, 3038 KiB  
Case Report
Single-Cell DNA Sequencing and Immunophenotypic Profiling to Track Clonal Evolution in an Acute Myeloid Leukemia Patient
by María García-Álvarez, Ana Yeguas, Cristina Jiménez, Alejandro Medina-Herrera, Verónica González-Calle, Montserrat Hernández-Ruano, Rebeca Maldonado, Irene Aires, Cristina Casquero, Inmaculada Sánchez-Villares, Ana Balanzategui, María Eugenia Sarasquete, Miguel Alcoceba, María Belén Vidriales, Marcos González-Díaz, Ramón García-Sanz and María Carmen Chillón
Biomedicines 2024, 12(1), 66; https://doi.org/10.3390/biomedicines12010066 - 27 Dec 2023
Viewed by 1062
Abstract
Single-cell DNA sequencing can address the sequence of somatic genetic events during myeloid transformation in relapsed acute myeloid leukemia (AML). We present an NPM1-mutated AML patient with an initial low ratio of FLT3-ITD (low-risk ELN-2017), treated with midostaurin combined with standard [...] Read more.
Single-cell DNA sequencing can address the sequence of somatic genetic events during myeloid transformation in relapsed acute myeloid leukemia (AML). We present an NPM1-mutated AML patient with an initial low ratio of FLT3-ITD (low-risk ELN-2017), treated with midostaurin combined with standard chemotherapy as front-line treatment, and with salvage therapy plus gilteritinib following allogenic stem cell transplantation after relapse. Simultaneous single-cell DNA sequencing and cell-surface immunophenotyping was used in diagnostic and relapse samples to understand the clinical scenario of this patient and to reconstruct the clonal composition of both tumors. Four independent clones were present before treatment: DNMT3A/DNMT3A/NPM1 (63.9%), DNMT3A/DNMT3A (13.9%), DNMT3A/DNMT3A/NPM1/FLT3 (13.8%), as well as a wild-type clone (8.3%), but only the minor clone with FLT3-ITD survived and expanded after therapy, being the most represented one (58.6%) at relapse. FLT3-ITD was subclonal and was found only in the myeloid blast population (CD38/CD117/CD123). Our study shows the usefulness of this approach to reveal the clonal architecture of the leukemia and the identification of small subclones at diagnosis and relapse that may explain how the neoplastic cells can escape from the activity of different treatments in a stepwise process that impedes the disease cure despite different stages of complete remission. Full article
(This article belongs to the Special Issue Molecular Research on Acute Myeloid Leukemia (AML) Volume II)
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