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Molecular Mechanisms and Therapies of Hematological Tumors

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: 20 July 2025 | Viewed by 1740

Special Issue Editors


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Guest Editor
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, FC, Italy
Interests: leukemia; diagnostic; MPN; NGS

E-Mail Website
Guest Editor
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, FC, Italy
Interests: acute myeloid leukemia; genomics; cell metabolism; targeted therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hematological malignancies consist of different cancers including leukemias, lymphomas, multiple myeloma, myeloproliferative neoplasms, and myelodysplastic syndromes. Recent advances in sequencing technologies have better defined the genomic landscape of hematological diseases and partially explained the molecular mechanisms underlying the carcinogenesis processes. This led to the development of different target therapies such as IDH inhibitors or BCL2 inhibitors that can be used beyond the standard chemotherapy to target and resolve the complexity of hematological disease and improve patient outcomes. Recently, the pathogenic roles of KMT2A rearrangements have been elucidated and patients characterized by this structural alteration can take advantage from Menin inhibitor use. Despite this, leukemic stem cells possess different relapse/refractory mechanisms, for example, multi-drug resistance, responsible for the relapse of disease.

This Special Issue aims to explain new insights into genetic and epigenetic alterations, cancer metabolism, target therapies, therapy response, drug resistance and relapse of the disease. Both original research articles, including in vitro studies, and reviews articles are strongly invited for submission.

Dr. Maria Teresa Bochicchio
Dr. Giorgia Simonetti
Guest Editors

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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.

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Keywords

  • genetic alterations
  • next-generation sequencing
  • molecular biomarkers
  • target therapy
  • drug resistance

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Published Papers (2 papers)

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Research

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22 pages, 4108 KiB  
Article
Targeting the p53/xCT/GSH Axis with PRIMA-1Met Combined with Sulfasalazine Shows Therapeutic Potential in Chronic Lymphocytic Leukemia
by Martina Pasino, Andrea Speciale, Silvia Ravera, Giovanna Cutrona, Rosanna Massara, Nadia Bertola, Maurizio Viale, Irena Velkova, Andrea Nicola Mazzarello, Franco Fais, Fabrizio Loiacono, Serena Matis, Giulia Elda Valenti, Nicola Traverso, Cinzia Domenicotti, Barbara Marengo, Bruno Tasso, Adalberto Ibatici, Emanuele Angelucci, Tiziana Vaisitti, Paola Monti and Paola Menichiniadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(12), 5559; https://doi.org/10.3390/ijms26125559 - 10 Jun 2025
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Abstract
In Chronic Lymphocytic Leukemia (CLL), mutations at the TP53 tumor suppressor gene are an important hallmark since they may strongly influence the therapeutic decision. PRIMA-1Met (also known as APR-246/Eprenetapopt) is a small molecule able to restore the wild-type (wt) p53 conformation to [...] Read more.
In Chronic Lymphocytic Leukemia (CLL), mutations at the TP53 tumor suppressor gene are an important hallmark since they may strongly influence the therapeutic decision. PRIMA-1Met (also known as APR-246/Eprenetapopt) is a small molecule able to restore the wild-type (wt) p53 conformation to mutant p53 proteins and to stimulate apoptosis in tumor cells; in addition, it can deplete the glutathione reservoir, increasing reactive oxygen species (ROS) production. In this study, we investigated whether combining PRIMA-1Met with Sulfasalazine (SAS), a SLC7A11/xCT inhibitor, reduces CLL cell viability by targeting mutant p53 and the glutathione pathway. The results demonstrated that, in CLL cells, PRIMA-1Met did not restore the wt functions in the mutant p53 proteins, but it strongly reduced the antioxidant defense and induced cell death. PRIMA-1Met and SAS combination synergistically reduced cell survival regardless of p53 status and further impaired antioxidant capacity, especially in mutant p53 cells, linking their cytotoxic effect to redox imbalance. Thus, the association of PRIMA-1Met with drugs targeting the antioxidant response could represent a valid strategy to kill CLL cells carrying either wt or mutant p53. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies of Hematological Tumors)
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Review

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26 pages, 1955 KiB  
Review
From Chemotherapy to Targeted Therapy: Unraveling Resistance in Acute Myeloid Leukemia Through Genetic and Non-Genetic Insights
by Shuting Cao, Qiuxia Wang and Ganqian Zhu
Int. J. Mol. Sci. 2025, 26(9), 4005; https://doi.org/10.3390/ijms26094005 - 24 Apr 2025
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Abstract
Acute myeloid leukemia (AML) is a devastating disease characterized by extensive inter-patient and intra-patient heterogeneity. Despite the introduction of intensive chemotherapy in the 1970s as the standard treatment, the development of mechanism-based targeted therapies since 2017 has been broadening the therapeutic landscape. However, [...] Read more.
Acute myeloid leukemia (AML) is a devastating disease characterized by extensive inter-patient and intra-patient heterogeneity. Despite the introduction of intensive chemotherapy in the 1970s as the standard treatment, the development of mechanism-based targeted therapies since 2017 has been broadening the therapeutic landscape. However, both chemotherapy and targeted therapies continue to face the challenges of primary and secondary resistance. This review summarizes the mechanisms underlying resistance to chemotherapy and targeted therapies in AML and discusses the opportunities and challenges brought by the transition from chemotherapy to precision medicine. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies of Hematological Tumors)
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