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Acute Myeloid Leukemia and Myelodysplastic Syndromes: Biological and Clinical Implications
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Acute Myeloid Leukemia and Myelodysplastic Syndromes: Biological and Clinical Implications

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 9336

Special Issue Editor

Dr. Sergiu Pasca

E-Mail Website
Guest Editor
Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj Napoca, Romania
Interests: hematology; data analysis; next generation sequencing; bioinformatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acute myeloid leukemia (AML) is a malignancy of the hematopoietic stem cell and is characterized biologically by the uncontrolled division and undifferentiated phenotype of the malignant cells. The main clinical characteristics of this disease are caused by bone marrow infiltration and inhibition of the normal hematopoietic lineages, leading, most frequently, to bone marrow insufficiency. Although, clinically, most AML subtypes have a similar presentation, it becomes more and more clear that AML is a general term a plethora of diseases. This can be seen with the World Health Organization (WHO) 2016 classification of AML and in the “boom” of new therapies approved for AML in the recent years for the different subtypes of disease. This being said, there are still a lot of AML subtypes with poor prognosis and that have no specific therapy.

Conversely, myelodysplastic syndrome (MDS) is also characterized by bone marrow insufficiency. Although, this is not caused in all cases by the presence of blasts, and rather it is represented by the influence that the bone marrow microenvironment has on the hematopoietic stem cell. Thus, MDS represents a heterogeneous entity in which the therapy did not see the “boom” that AML experienced.

Because of the aforementioned arguments, both of these types of disease still need more research to better understand their biology and how this can be translated in the clinical scenario.

Thus, the current Special Issue will be focused on the biological and clinical characteristics of AML and MDS, trying to further advance the understanding of these entities and, ultimately, offer stepping stones for a better clinical management.

Dr. Sergiu Pasca
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. Medicina 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 1800 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
  • myelodysplastic syndrome
  • translational medicine

Published Papers (3 papers)

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Research

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12 pages, 3437 KiB  
Article
TET2/IDH1/2/WT1 and NPM1 Mutations Influence the RUNX1 Expression Correlations in Acute Myeloid Leukemia
by Sergiu Pasca, Ancuta Jurj, Ciprian Tomuleasa and Mihnea Zdrenghea
Medicina 2020, 56(12), 637; https://doi.org/10.3390/medicina56120637 - 24 Nov 2020
Cited by 1 | Viewed by 1909
Abstract
Background and objectives: Mutational analysis has led to a better understanding of acute myeloid leukemia (AML) biology and to an improvement in clinical management. Some of the most important mutations that affect AML biology are represented by mutations in genes related to methylation, [...] Read more.
Background and objectives: Mutational analysis has led to a better understanding of acute myeloid leukemia (AML) biology and to an improvement in clinical management. Some of the most important mutations that affect AML biology are represented by mutations in genes related to methylation, more specifically: TET2, IDH1, IDH2 and WT1. Because it has been shown in numerous studies that mutations in these genes lead to similar expression profiles and phenotypes in AML, we decided to assess if mutations in any of those genes interact with other genes important for AML. Materials and Methods: We downloaded the clinical data, mutational profile and expression profile from the TCGA LAML dataset via cBioPortal. Data were analyzed using classical statistical methods and functional enrichment analysis software represented by STRING and GOrilla. Results: The first step we took was to assess the 196 AML cases that had a mutational profile available and observe the mutations that overlapped with TET2/IDH1/2/WT1 mutations. We observed that RUNX1 mutations significantly overlap with TET2/IDH1/2/WT1 mutations. Because of this, we decided to further investigate the role of RUNX1 mutations in modulating the level of RUNX1 mRNA and observed that RUNX1 mutant cases presented higher levels of RUNX1 mRNA. Because there were only 16 cases of RUNX1 mutant samples and that mutations in this gene determined a change in mRNA expression, we further observed the correlation between RUNX1 and other mRNAs in subgroups regarding the presence of hypermethylating mutations and NPM1. Here, we observed that both TET2/IDH1/2/WT1 and NPM1 mutations increase the number of genes negatively correlated with RUNX1 and that these genes were significantly linked to myeloid activation. Conclusions: In the current study, we have shown that NPM1 and TET2/IDH1/2/WT1 mutations increase the number of negative correlations of RUNX1 with other transcripts involved in myeloid differentiation. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia and Myelodysplastic Syndromes: Biological and Clinical Implications)
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14 pages, 1224 KiB  
Article
A Pilot Study of Circulating Monocyte Subsets in Patients Treated with Stem Cell Transplantation for High-Risk Hematological Malignancies
by Ida Marie Rundgren, Elisabeth Ersvær, Aymen Bushra Ahmed, Anita Ryningen and Øystein Bruserud
Medicina 2020, 56(1), 36; https://doi.org/10.3390/medicina56010036 - 18 Jan 2020
Cited by 4 | Viewed by 2034
Abstract
Background and Objectives: Autologous and allogeneic stem cell transplantation is used in the treatment of high-risk hematological malignancies, and monocytes are probably involved in hematological reconstitution as well as posttransplant immunoregulation. The aim of our study was to investigate the levels of circulating [...] Read more.
Background and Objectives: Autologous and allogeneic stem cell transplantation is used in the treatment of high-risk hematological malignancies, and monocytes are probably involved in hematological reconstitution as well as posttransplant immunoregulation. The aim of our study was to investigate the levels of circulating monocyte subsets in allotransplant recipients. Materials and Methods: The levels of the classical, intermediate, and nonclassical monocyte subsets were determined by flow cytometry. Sixteen patients and 18 healthy controls were included, and the levels were analyzed during pretransplant remission (n = 13), early posttransplant during cytopenia (n = 9), and early reconstitution (n = 9). Results: Most patients in remission showed a majority of classical monocytes. The patients showed severe early posttransplant monocytopenia, but the total peripheral blood monocyte counts normalized very early on, and before neutrophil and platelet counts. During the first 7–10 days posttransplant (i.e., during cytopenia) a majority of the circulating monocytes showed a nonclassical phenotype, but later (i.e., 12–28 days posttransplant) the majority showed a classical phenotype. However, the variation range of classical monocytes was wider for patients in remission and during regeneration than for healthy controls. Conclusions: The total peripheral blood monocyte levels normalize at the very early stages and before neutrophil reconstitution after stem cell transplantation, and a dominance of classical monocytes is reached within 2–4 weeks posttransplant. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia and Myelodysplastic Syndromes: Biological and Clinical Implications)
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Review

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16 pages, 373 KiB  
Review
Prognostic Markers of Myelodysplastic Syndromes
by Yuliya Andreevna Veryaskina, Sergei Evgenievich Titov, Igor Borisovich Kovynev, Tatiana Ivanovna Pospelova and Igor Fyodorovich Zhimulev
Medicina 2020, 56(8), 376; https://doi.org/10.3390/medicina56080376 - 27 Jul 2020
Cited by 8 | Viewed by 4939
Abstract
Myelodysplastic syndrome (MDS) is a clonal disease characterized by multilineage dysplasia, peripheral blood cytopenias, and a high risk of transformation to acute myeloid leukemia. In theory, from clonal hematopoiesis of indeterminate potential to hematologic malignancies, there is a complex interplay between genetic and [...] Read more.
Myelodysplastic syndrome (MDS) is a clonal disease characterized by multilineage dysplasia, peripheral blood cytopenias, and a high risk of transformation to acute myeloid leukemia. In theory, from clonal hematopoiesis of indeterminate potential to hematologic malignancies, there is a complex interplay between genetic and epigenetic factors, including miRNA. In practice, karyotype analysis assigns patients to different prognostic groups, and mutations are often associated with a particular disease phenotype. Among myeloproliferative disorders, secondary MDS is a group of special entities with a typical spectrum of genetic mutations and cytogenetic rearrangements resembling those in de novo MDS. This overview analyzes the present prognostic systems of MDS and the most recent efforts in the search for genetic and epigenetic markers for the diagnosis and prognosis of MDS. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia and Myelodysplastic Syndromes: Biological and Clinical Implications)
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