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Novel Therapeutics and Therapeutic Resistance in Hematological Malignancy

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: closed (31 December 2023) | Viewed by 3452

Special Issue Editors


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Guest Editor
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, 47014 Meldola, Italy
Interests: acute lymphoblastic leukemia; acute myeloid leukemia; myelodysplastic syndromes; multiple myeloma and MGUS; non-Hodgkin and Hodgkin lymphoma
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Special Issue Information

Dear Colleagues,

The last few years have ushered in a new era of hematological malignancy research; the advent and approval of multiple targeted therapies and an improved understanding of patient immune systems have resulted in major progress in the development of immune therapies, including monoclonal antibodies with and without conjugated toxins (bacterial or chemical), bispecific T-cell engagers and DART antibodies, immune-checkpoint-based therapies, and CAR-T cell approaches.

At the same time, tumor biology has also seen recent advancements, leading to new combinations of drugs and novel therapies.

The numerous ongoing trials evaluating these therapies, with well-designed correlative interrogation of the immune system in patients treated in such trials, will further enhance our understanding of immune therapies with both single-agent and combination approaches.

This Special Issue will focus on personalized medicine in hematology, the efficacy of novel therapeutics, and promising combination approaches for further improving patient treatment outcomes.

Dr. Claudio Cerchione
Dr. Giovanni Martinelli
Guest Editors

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Keywords

  • hematology
  • hematological malignancies
  • novel agents
  • target therapy
  • multiple myeloma
  • leukemia
  • acute leukemia
  • chronic leukemia
  • non-Hodgkin lymphoma
  • Hodgkin lymphoma

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Published Papers (2 papers)

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Research

27 pages, 4835 KiB  
Article
Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production
by Carlos Ramos-Acosta, Laura Huerta-Pantoja, Milton Eduardo Salazar-Hidalgo, Elsa Mayol, Selene Jiménez-Vega, Pablo García-Peña, Jenifeer Jordi-Cruz, Cristina Baquero, Almudena Porras, Belén Íñigo-Rodríguez, Celina M. Benavente, Andrea R. López-Pastor, Irene Gómez-Delgado, Elena Urcelay, Francisco Javier Candel and Eduardo Anguita
Int. J. Mol. Sci. 2024, 25(9), 4887; https://doi.org/10.3390/ijms25094887 - 30 Apr 2024
Viewed by 1367
Abstract
Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. [...] Read more.
Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment. Full article
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18 pages, 6974 KiB  
Article
5-Aza-2′-Deoxycytidine Alters the Methylation Profile of Bortezomib-Resistant U266 Multiple Myeloma Cells and Affects Their Proliferative Potential
by Karolina Łuczkowska, Piotr Kulig, Klaudia Rusińska, Bartłomiej Baumert and Bogusław Machaliński
Int. J. Mol. Sci. 2023, 24(23), 16780; https://doi.org/10.3390/ijms242316780 - 26 Nov 2023
Cited by 2 | Viewed by 1356
Abstract
Multiple myeloma (MM) is a plasma cell malignancy that accounts for 1% of all cancers and is the second-most-common hematological neoplasm. Bortezomib (BTZ) is a proteasome inhibitor widely implemented in the treatment of MM alone or in combination with other agents. The development [...] Read more.
Multiple myeloma (MM) is a plasma cell malignancy that accounts for 1% of all cancers and is the second-most-common hematological neoplasm. Bortezomib (BTZ) is a proteasome inhibitor widely implemented in the treatment of MM alone or in combination with other agents. The development of resistance to chemotherapy is one of the greatest challenges of modern oncology. Therefore, it is crucial to discover and implement new adjuvant therapies that can bypass therapeutic resistance. In this paper, we investigated the in vitro effect of methylation inhibitor 5-Aza-2′-deoxycytidine on the proliferative potential of MM cells and the development of resistance to BTZ. We demonstrate that alterations in the DNA methylation profile are associated with BTZ resistance. Moreover, the addition of methylation inhibitor 5-Aza-2′-deoxycytidine to BTZ-resistant MM cells led to a reduction in the proliferation of the BTZ-resistant phenotype, resulting in the restoration of sensitivity to BTZ. However, further in vitro and ex vivo studies are required before adjuvant therapy can be incorporated into existing treatment regimens. Full article
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