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Genomic Oncology and Medicine in Leukemia: From Molecular Pathogenesis to Novel Therapeutic Approaches

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 July 2024 | Viewed by 3539

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Special Issue Editor

Dr. Yosuke Minami

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Guest Editor

National Cancer Center Hospital East, Kashiwa 277-8577, Chiba, Japan
Interests: leukemia; molecular target therapy; precision medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Leukemia is an aggressive hematologic malignancy often characterized by specific genomic alterations. The standard treatment strategy for acute leukemia largely comprises intensive chemotherapy with or without hematopoietic stem cell transplantation. However, long-term survival can be achieved in only up to approximately three-quarters of patients, even in the favorable risk group. Molecular-targeted therapy has had a significant impact on clinical practice, especially for patients with specific genomic abnormalities such as FLT3- and IDH1/2-mutations. In this Special Issue, our focus is on the cutting edge of genomic oncology and precision medicine in leukemia, and the progress from molecular pathogenesis to novel therapeutic approaches.

Dr. Yosuke Minami
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

leukemia
genomic oncology
precision medicine
molecular biomarker
molecular targeted therapy

Published Papers (3 papers)

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Research

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23 pages, 4786 KiB

Open AccessArticle

FL118 Is a Potent Therapeutic Agent against Chronic Myeloid Leukemia Resistant to BCR-ABL Inhibitors through Targeting RNA Helicase DDX5

by Kengo Takeda, Satoshi Ohta, Miu Nagao, Erika Kobayashi, Kenji Tago and Megumi Funakoshi-Tago

Int. J. Mol. Sci. 2024, 25(7), 3693; https://doi.org/10.3390/ijms25073693 - 26 Mar 2024

Viewed by 612

Abstract

Chronic myeloid leukemia (CML) is induced by the expression of the fused tyrosine kinase BCR-ABL, which is caused by a chromosomal translocation. BCR-ABL inhibitors have been used to treat CML; however, the acquisition of resistance by CML cells during treatment is a serious issue. We herein demonstrated that BCR-ABL induced the expression of the RNA helicase DDX5 in K562 cells derived from CML patients in a manner that was dependent on its kinase activity, which resulted in cell proliferation and survival. The knockout of DDX5 decreased the expression of BIRC5 (survivin) and activated caspase 3, leading to apoptosis in K562 cells. Similar results were obtained in cells treated with FL118, an inhibitor of DDX5 and a derivative compound of camptothecin (CPT). Furthermore, FL118 potently induced apoptosis not only in Ba/F3 cells expressing BCR-ABL, but also in those expressing the BCR-ABL T315I mutant, which is resistant to BCR-ABL inhibitors. Collectively, these results revealed that DDX5 is a critical therapeutic target in CML and that FL118 is an effective candidate compound for the treatment of BCR-ABL inhibitor-resistant CML. Full article

(This article belongs to the Special Issue Genomic Oncology and Medicine in Leukemia: From Molecular Pathogenesis to Novel Therapeutic Approaches)

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14 pages, 785 KiB

Open AccessArticle

Comprehensive Molecular Profiling of NPM1-Mutated Acute Myeloid Leukemia Using RNAseq Approach

by Jessica Petiti, Ymera Pignochino, Aurora Schiavon, Emilia Giugliano, Enrico Berrino, Giorgia Giordano, Federico Itri, Matteo Dragani, Daniela Cilloni and Marco Lo Iacono

Int. J. Mol. Sci. 2024, 25(7), 3631; https://doi.org/10.3390/ijms25073631 - 24 Mar 2024

Viewed by 743

Abstract

Acute myeloid leukemia (AML) is a complex hematologic malignancy with high morbidity and mortality. Nucleophosmin 1 (NPM1) mutations occur in approximately 30% of AML cases, and NPM1-mutated AML is classified as a distinct entity. NPM1-mutated AML patients without additional genetic abnormalities have a favorable prognosis. Despite this, 30–50% of them experience relapse. This study aimed to investigate the potential of total RNAseq in improving the characterization of NPM1-mutated AML patients. We explored genetic variations independently of myeloid stratification, revealing a complex molecular scenario. We showed that total RNAseq enables the uncovering of different genetic alterations and clonal subtypes, allowing for a comprehensive evaluation of the real expression of exome transcripts in leukemic clones and the identification of aberrant fusion transcripts. This characterization may enhance understanding and guide improved treatment strategies for NPM1mut AML patients, contributing to better outcomes. Our findings underscore the complexity of NPM1-mutated AML, supporting the incorporation of advanced technologies for precise risk stratification and personalized therapeutic strategies. The study provides a foundation for future investigations into the clinical implications of identified genetic variations and highlights the importance of evolving diagnostic approaches in leukemia management. Full article

(This article belongs to the Special Issue Genomic Oncology and Medicine in Leukemia: From Molecular Pathogenesis to Novel Therapeutic Approaches)

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Review

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28 pages, 2016 KiB

Open AccessReview

Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome

by Hironori Arai, Hirotaka Matsui, SungGi Chi, Yoshikazu Utsu, Shinichi Masuda, Nobuyuki Aotsuka and Yosuke Minami

Int. J. Mol. Sci. 2024, 25(1), 652; https://doi.org/10.3390/ijms25010652 - 4 Jan 2024

Cited by 1 | Viewed by 1690

Abstract

Due to the proliferation of genetic testing, pathogenic germline variants predisposing to hereditary hematological malignancy syndrome (HHMS) have been identified in an increasing number of genes. Consequently, the field of HHMS is gaining recognition among clinicians and scientists worldwide. Patients with germline genetic abnormalities often have poor outcomes and are candidates for allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT using blood from a related donor should be carefully considered because of the risk that the patient may inherit a pathogenic variant. At present, we now face the challenge of incorporating these advances into clinical practice for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and optimizing the management and surveillance of patients and asymptomatic carriers, with the limitation that evidence-based guidelines are often inadequate. The 2016 revision of the WHO classification added a new section on myeloid malignant neoplasms, including MDS and AML with germline predisposition. The main syndromes can be classified into three groups. Those without pre-existing disease or organ dysfunction; DDX41, TP53, CEBPA, those with pre-existing platelet disorders; ANKRD26, ETV6, RUNX1, and those with other organ dysfunctions; SAMD9/SAMD9L, GATA2, and inherited bone marrow failure syndromes. In this review, we will outline the role of the genes involved in HHMS in order to clarify our understanding of HHMS. Full article

(This article belongs to the Special Issue Genomic Oncology and Medicine in Leukemia: From Molecular Pathogenesis to Novel Therapeutic Approaches)

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