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Current Topics in Acute Myeloid Leukemia
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Current Topics in Acute Myeloid Leukemia

A special issue of Hemato (ISSN 2673-6357). This special issue belongs to the section "Leukemias".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 14986

Special Issue Editors

Dr. Ugo Testa

E-Mail
Guest Editor
Department of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
Interests: acute myeloid leukemia; normal and leukemic stem cells; hematopoietic differentiation; cell differentiation therapy; targeted therapy; CD123 targeting
Special Issues, Collections and Topics in MDPI journals
Dr. Roland B. Walter

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Guest Editor
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA
Interests: acute myeloid leukemia; antibody-based therapy; CD33; clinical trials; minimal residual disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The principles of modern curative-intent therapy for acute myeloid leukemia (AML) were established in the early 1970s with the introduction of intensive combination chemotherapy with cytarabine and an anthracycline (“7+3”). With advancements in supportive care and refinements in the delivery of hematopoietic cell transplantation (HCT), treatment outcomes have gradually improved over the past 5 decades, particularly for children and younger adults. The treatment landscape is currently rapidly changing. Paralleling an increased understanding of the genetic heterogeneity of AML and its prognostic implications, there are now several new drugs approved, expanding the therapeutic options for patients affected by this malignancy. This Special Issue will highlight some of the current topics in AML related to the changes in the treatment algorithm.

Dr. Ugo Testa
Dr. Roland B. Walter
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 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. Hemato is an international peer-reviewed open access quarterly 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 1000 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 
  • Cellular therapies 
  • Hematopoietic cell transplantation 
  • Induction chemotherapy 
  • Maintenance therapy 
  • Novel therapeutics 
  • Supportive care 
  • Treatment algorithm

Published Papers (5 papers)

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Review

26 pages, 845 KiB  
Review
Genome-Based Medicine for Acute Myeloid Leukemia: Study and Targeting of Molecular Alterations and Use of Minimal Residual Disease as a Biomarker
by Ugo Testa, Germana Castelli and Elvira Pelosi
Hemato 2022, 3(3), 543-568; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato3030038 - 06 Sep 2022
Viewed by 1800
Abstract
Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy characterized by the clonal proliferation of hematopoietic stem and progenitor cells (HSPCs) and blockade of differentiation and proliferation of immature myeloid cells that accumulate in bone marrow at the expense of normal hematopoiesis. [...] Read more.
Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy characterized by the clonal proliferation of hematopoietic stem and progenitor cells (HSPCs) and blockade of differentiation and proliferation of immature myeloid cells that accumulate in bone marrow at the expense of normal hematopoiesis. AMLs originate from the expansion of HSPCs progressively acquiring somatic mutations. The development of high-throughput sequencing techniques has helped to discover the genetic heterogeneity and complexity of AMLs, revise diagnostic and prognostic criteria, and to identify new therapeutic targets. These studies have allowed the identification of several recurrent driver mutations and the definition of a rational molecular classification of these tumors. In parallel, the development of techniques for the determination of single-cell mutational profiling has considerably contributed to understanding the clonal heterogeneity and evolution of AMLs. The acquisition of these genetic data coupled with the identification of molecular therapeutic targets has determined a considerable expansion of the therapeutic armamentarium, with the development of several new drugs highly active against specific AML subtypes. These developments have increased the interest and the need for sensitive techniques for the identification of minimal residual disease, the population of leukemia cells that survives despite morphological remission and causes disease relapse. Full article
(This article belongs to the Special Issue Current Topics in Acute Myeloid Leukemia)
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16 pages, 330 KiB  
Review
The Current Understanding of and Treatment Paradigm for Newly-Diagnosed TP53-Mutated Acute Myeloid Leukemia
by Rory M. Shallis, Maximilian Stahl, Jan Philipp Bewersdorf and Amer M. Zeidan
Hemato 2021, 2(4), 748-763; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2040051 - 09 Dec 2021
Cited by 2 | Viewed by 2790
Abstract
About 10% of newly diagnosed and 20–30% of therapy-related acute myeloid leukemia (AML) harbors a TP53 mutation (mTP53-AML). Unfortunately, this biological subset predicts one of the worst prognoses among patients with AML, specifically a median overall survival of about 7 months [...] Read more.
About 10% of newly diagnosed and 20–30% of therapy-related acute myeloid leukemia (AML) harbors a TP53 mutation (mTP53-AML). Unfortunately, this biological subset predicts one of the worst prognoses among patients with AML, specifically a median overall survival of about 7 months with fewer than 10% of patients eventually cured of disease. Although remission rates appear to be increased with venetoclax-based, less-intensive regimens when compared with contemporary, intensive chemotherapy (55–65% vs. 40%), survival appears to be no different between the two approaches. Attempts to discern whether or not the prognosis of mTP53-AML is universally poor have centered around the study of concurrent cytogenetic risk and predicted TP53 allelic state, measurable residual disease status and the impact of conditioning intensity for patients proceeding to allogeneic hematopoietic stem cell transplantation. We discuss these considerations in this review and offer the current treatment approach to TP53-mutated AML. Full article
(This article belongs to the Special Issue Current Topics in Acute Myeloid Leukemia)
16 pages, 1890 KiB  
Review
Transcriptional Regulation by the NFAT Family in Acute Myeloid Leukaemia
by Shaun D. Patterson, Xu Huang, Heather G. Jørgensen and Alison M. Michie
Hemato 2021, 2(3), 556-571; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2030035 - 27 Aug 2021
Cited by 4 | Viewed by 3405
Abstract
Acute myeloid leukaemia (AML) is a haematological cancer with poor outcomes due to a lack of efficacious targeted therapies. The Nuclear Factor of Activated T Cells (NFAT) family of transcription factors is well characterised as a regulator of the cell cycle and differentiation [...] Read more.
Acute myeloid leukaemia (AML) is a haematological cancer with poor outcomes due to a lack of efficacious targeted therapies. The Nuclear Factor of Activated T Cells (NFAT) family of transcription factors is well characterised as a regulator of the cell cycle and differentiation in the myeloid lineage. Recent evidence has demonstrated that NFAT family members may have roles in regulating AML leukemogenesis and resistance to targeted therapy in myeloid leukaemia. Furthermore, gene expression data from patient samples show that some NFATs are more highly expressed in poorly differentiated AML and after disease relapse, implying that the NFAT family may have roles in specific types of AML. This review outlines the evidence for the role of NFAT in healthy myeloid tissue and explores how NFAT might regulate AML pathogenesis, highlighting the potential to target specific NFAT proteins therapeutically in AML. Full article
(This article belongs to the Special Issue Current Topics in Acute Myeloid Leukemia)
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37 pages, 411 KiB  
Review
Trials and Tribulations in the Frontline Treatment of Older Adults with Acute Myeloid Leukemia
by Adam S. Zayac and John L. Reagan
Hemato 2021, 2(3), 515-544; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2030033 - 18 Aug 2021
Viewed by 2227
Abstract
Acute myeloid leukemia (AML) is a heterogeneous aggressive hematologic malignancy derived from malignant clones that promote their own growth and survival at the expense of normal hematopoiesis resulting in life-threatening bleeding and infections. Traditional initial AML therapy has been centered on a backbone [...] Read more.
Acute myeloid leukemia (AML) is a heterogeneous aggressive hematologic malignancy derived from malignant clones that promote their own growth and survival at the expense of normal hematopoiesis resulting in life-threatening bleeding and infections. Traditional initial AML therapy has been centered on a backbone of intensive chemotherapy often composed of an anthracycline and cytarabine. This strategy has proven most effective in patients less than 60 years of age due to both patient-related tolerability factors as well as changes in AML biology centered on chemotherapy refractory mutational profiles that are seen with advancing age. Recent improvements in frontline AML therapy have been seen in patients 60 years of age and over, a population most typically referred to as “older” adult AML. Herein, we describe the characteristics of “older” adult AML, review the differences in outcomes amongst those 60–75 and those over 75 years of age, and cite challenges in delivering frontline therapies within this group based not only on therapeutic toxicity but also on the patient’s overall level of “fitness” and inherent biology. We also discuss the role of targeted therapies that inhibit specific mutations and have the potential to deliver improved efficacy with less side effects while also recognizing that some selected older AML patients still benefit from intensive induction therapy. Full article
(This article belongs to the Special Issue Current Topics in Acute Myeloid Leukemia)
23 pages, 2071 KiB  
Review
Precision Medicine Treatment in Acute Myeloid Leukemia Is Not a Dream
by Ugo Testa, Elvira Pelosi and Germana Castelli
Hemato 2021, 2(1), 131-153; https://0-doi-org.brum.beds.ac.uk/10.3390/hemato2010008 - 04 Mar 2021
Cited by 3 | Viewed by 3243
Abstract
The development of molecular studies to define the somatic genetic alterations has revolutionized the diagnostic and therapeutic management of acute myeloid leukemia (AML). AML is a highly heterogenous disease that includes many molecular subtypes; each subtype is heterogeneous both for the presence of [...] Read more.
The development of molecular studies to define the somatic genetic alterations has revolutionized the diagnostic and therapeutic management of acute myeloid leukemia (AML). AML is a highly heterogenous disease that includes many molecular subtypes; each subtype is heterogeneous both for the presence of variable co-mutations and complex combinations of clones and subclones, changing during disease evolution and in response to treatment. The treatment of AML is changing from standardized schemes of induction and consolidation chemotherapy to tailored approaches according to molecular and genetic profiles and to targeted therapy. Several molecularly targeted therapies have been approved for the treatment of some AML patients, including mutation-specific targeted drugs such as FLT3, IDH1 and IDH2 inhibitors, mutation-independent targeted drugs such as the Bcl2 inhibitor venetoclax, the hedgehog inhibitor glasdegib and the CD33-targeted drug gemtuzumab ozogamicin. Furthermore, recent studies have shown the feasibility of a personalized medicine approach for the treatment of AML patients, where the therapy decisions are guided by the results of genomic studies. Full article
(This article belongs to the Special Issue Current Topics in Acute Myeloid Leukemia)
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