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Molecular Biology and Targeted Therapies in Leukemias
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Molecular Biology and Targeted Therapies in Leukemias

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 1892

Special Issue Editors

Dr. Fabio Stagno

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Guest Editor
Hematology Unit, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy
Interests: chronic myeloid leukemia; flow cytometry; multidrug resistance; BCR-ABL1 oncogene
Special Issues, Collections and Topics in MDPI journals
Dr. Stefania Stella

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Guest Editor
Center of Experimental Onco-Hematology (COES), Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, CT, Italy
Interests: oncology; hematology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent decades, new advances in molecular biology have furthered our understanding of the mechanisms of several types of leukemias and enhanced our molecular and clinical knowledge. Investigations on several genetic driver mutations, oncogenes, tumor suppressor genes, epigenetic changes and signaling pathways have lead to the development of new drugs that specifically target the molecular and genetic abnormalities underlying distinct types of leukemia. Therefore, target therapy is revolutionizing classical leukemia treatments, aiming to improve clinical outcomes by selectively targeting leukemia cells and minimizing the damage to normal tissue cells. The introduction of tyrosine kinase inhibitors, FLT3 and BCL-2 inhibitors, epigenetic modulators and CAR-T cell therapies into the clinical therapeutic scenario has enhanced clinical progress. This Special Issue will focus on both the biomolecular mechanisms and the efficacy of novel target treatments in leukemias through showcasing original research articles and reviews.

Dr. Fabio Stagno
Dr. Stefania Stella
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. 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

  • molecular biology
  • target therapy
  • leukemia
  • TKI
  • BCL-2
  • FLT3
  • CAR-T cells
  • CML

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Published Papers (2 papers)

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Research

9 pages, 1663 KiB  
Communication
No Benefit from Hydroxyurea Pre-Treatment in Frontline Chronic Myeloid Leukemia Therapy and Evidence of Quantitative Changes in the BCR::ABL1 Transcript Level
by Fabio Stagno, Stefania Stella, Salvatore Leotta, Santino Caserta, Silvia Rita Vitale, Uros Markovic, Cristina Tomarchio, Giuseppe Mirabile, Sabina Russo, Michele Massimino, Paolo Vigneri, Livia Manzella, Francesco Di Raimondo and Alessandro Allegra
Int. J. Mol. Sci. 2025, 26(5), 1840; https://doi.org/10.3390/ijms26051840 - 21 Feb 2025
Viewed by 437
Abstract
Hydroxyurea (HU) cytoreduction is usually administered to patients with chronic myeloid leukemia before starting any tyrosine kinase inhibitors (TKIs) therapy. However, up to date, there is no evidence of any benefit of hydroxyurea pre-treatment. Conversely, evidence has been provided on both the prognostic [...] Read more.
Hydroxyurea (HU) cytoreduction is usually administered to patients with chronic myeloid leukemia before starting any tyrosine kinase inhibitors (TKIs) therapy. However, up to date, there is no evidence of any benefit of hydroxyurea pre-treatment. Conversely, evidence has been provided on both the prognostic significance of the quantitative assessment of BCR::ABL1 expression at diagnosis and the individual decline of the BCR::ABL1 slope. In this view, we assumed that any kind of treatment administered before a confirmed diagnosis of chronic myeloid leukemia might change the amount of BCR::ABL1 transcript levels. To this purpose, we evaluated leukocyte counts and BCR::ABL1 quantitative expression either at diagnosis (baseline and no therapy) and on day 7 and day 14 of treatment in a cohort of 45 unselected patients with newly diagnosed chronic myeloid leukemia in the chronic phase. After informed consent, 21 of them received HU cytoreduction for 14 days before starting TKI treatment (HU group), whereas the other 24 patients received frontline TKI therapy without HU pre-treatment (TKI group). Our findings showed that: (i) there is no benefit from HU cytoreduction in patients affected with chronic myeloid leukemia before starting treatment with TKIs; (ii) any kind of therapy administered before a confirmed diagnosis of chronic myeloid leukemia might change the amount of BCR::ABL1 expression levels. Full article
(This article belongs to the Special Issue Molecular Biology and Targeted Therapies in Leukemias)
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12 pages, 1846 KiB  
Article
Proteasome Inhibitors Induce Apoptosis in Ex Vivo Cells of T-Cell Prolymphocytic Leukemia
by Vanessa Rebecca Gasparini, Elisa Rampazzo, Gregorio Barilà, Alessia Buratin, Elena Buson, Giulia Calabretto, Cristina Vicenzetto, Silvia Orsi, Alessia Tonini, Antonella Teramo, Livio Trentin, Monica Facco, Gianpietro Semenzato, Stefania Bortoluzzi and Renato Zambello
Int. J. Mol. Sci. 2024, 25(24), 13573; https://doi.org/10.3390/ijms252413573 - 18 Dec 2024
Viewed by 800
Abstract
Finding an effective treatment for T-PLL patients remains a significant challenge. Alemtuzumab, currently the gold standard, is insufficient in managing the aggressiveness of the disease in the long term. Consequently, numerous efforts are underway to address this unmet clinical need. The rarity of [...] Read more.
Finding an effective treatment for T-PLL patients remains a significant challenge. Alemtuzumab, currently the gold standard, is insufficient in managing the aggressiveness of the disease in the long term. Consequently, numerous efforts are underway to address this unmet clinical need. The rarity of the disease limits the ability to conduct robust clinical trials, making in silico, ex vivo, and in vivo drug screenings essential for designing new therapeutic strategies for T-PLL. We conducted a drug repurposing analysis based on T-PLL gene expression data and identified proteasome inhibitors (PIs) as a promising new class of compounds capable of reversing the T-PLL phenotype. Treatment of ex vivo T-PLL cells with Bortezomib and Carfilzomib, two PI compounds, supported this hypothesis by demonstrating increased apoptosis in leukemic cells. The current lack of a suitable in vitro model for the study of T-PLL prompted us to perform similar experiments in the SUP-T11 cell line, validating its potential by showing an increased apoptotic rate. Taken together, these findings open new avenues for investigating the molecular mechanisms underlying the efficacy of PI in T-PLL and expand the spectrum of potential therapeutic strategies for this highly aggressive disease. Full article
(This article belongs to the Special Issue Molecular Biology and Targeted Therapies in Leukemias)
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