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Recent Developments and Updates in Acute Lymphoblastic Leukemia

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 12110

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Special Issue Editor

Dr. Spiros Vlahopoulos

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Guest Editor

First Department of Paediatrics, National and Kapodistrian University of Athens, 157 72 Athens, Greece
Interests: acute myeloid leukemia; acute lymphoblastic leukemia

Special Issue Information

Dear Colleagues,

In spite of the generally favorable prognosis for Acute lymphoblastic leukemia, a portion of the patients succumb to the disease. This has been attributed to a number of factors, either linked to biological manifestations of the leukemic cells, or to factors associated with disrupted coordination and function of the host immune system. The latter is the field of some of the most exciting developments in cancer treatment, especially applicable in acute lymphoblastic leukemia. What is important, though, is to emphasize that signaling, development, homeostasis, immunity, and metabolism are functionally interdependent and therefore one holds a key to understanding the aberrations of the other.

In this Special Issue, we invite manuscripts with a focus on developments toward understanding and confronting acute lymphoblastic leukemia and its’ associated pathology at the molecular level, and extending from that.

Dr. Spiros Vlahopoulos
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

acute lymphoblastic leukemia
molecular biology
development
metabolism
immunity

Published Papers (6 papers)

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Research

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18 pages, 4745 KiB

Open AccessCommunication

Structural Analysis of Janus Tyrosine Kinase Variants in Hematological Malignancies: Implications for Drug Development and Opportunities for Novel Therapeutic Strategies

by Omar J. Rodriguez Moncivais, Stephanie A. Chavez, Victor H. Estrada Jimenez, Shengjie Sun, Lin Li, Robert A. Kirken and Georgialina Rodriguez

Int. J. Mol. Sci. 2023, 24(19), 14573; https://doi.org/10.3390/ijms241914573 - 26 Sep 2023

Cited by 3 | Viewed by 994

Abstract

Janus tyrosine kinase (JAK) variants are known drivers for hematological disorders. With the full-length structure of mouse JAK1 being recently resolved, new observations on the localization of variants within closed, open, and dimerized JAK structures are possible. Full-length homology models of human wild-type JAK family members were developed using the Glassman et al. reported mouse JAK1 containing the V658F structure as a template. Many mutational sites related to proliferative hematological disorders reside in the JH2 pseudokinase domains facing the region important in dimerization of JAKs in both closed and open states. More than half of all JAK gain of function (GoF) variants are changes in polarity, while only 1.2% are associated with a change in charge. Within a JAK1-JAK3 homodimer model, IFNLR1 (PDB ID7T6F) and the IL-2 common gamma chain subunit (IL2Rγc) were aligned with the respective dimer implementing SWISS-MODEL coupled with ChimeraX. JAK3 variants were observed to encircle the catalytic site of the kinase domain, while mutations in the pseudokinase domain align along the JAK-JAK dimerization axis. FERM domains of JAK1 and JAK3 are identified as a hot spot for hematologic malignancies. Herein, we propose new allosteric surfaces for targeting hyperactive JAK dimers. Full article

(This article belongs to the Special Issue Recent Developments and Updates in Acute Lymphoblastic Leukemia)

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15 pages, 1742 KiB

Open AccessArticle

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia

by José Vicente Gil, Esperanza Such, Claudia Sargas, Javier Simarro, Alberto Miralles, Gema Pérez, Inmaculada de Juan, Sarai Palanca, Gayane Avetisyan, Marta Santiago, Carolina Fuentes, José María Fernández, Ana Isabel Vicente, Samuel Romero, Marta Llop and Eva Barragán

Int. J. Mol. Sci. 2023, 24(5), 4440; https://doi.org/10.3390/ijms24054440 - 23 Feb 2023

Cited by 1 | Viewed by 2020

Abstract

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion–deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings. Full article

(This article belongs to the Special Issue Recent Developments and Updates in Acute Lymphoblastic Leukemia)

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Figure 1

12 pages, 2796 KiB

Open AccessArticle

A Novel Form of Arginine-Chitosan as Nanoparticles Efficient for siRNA Delivery into Mouse Leukemia Cells

by Jixian Luo, Jiangfeng Chen, Yan Liu, Yongji He and Wenjuan Dong

Int. J. Mol. Sci. 2023, 24(2), 1040; https://doi.org/10.3390/ijms24021040 - 05 Jan 2023

Cited by 3 | Viewed by 1725

Abstract

The modification of chitosan (CS) has greatly expanded its application in the field of medicine. In this study, low-molecular-weight chitosan was modified with arginine (Arg) by a simple method. The identification by the Fourier transform infrared spectra (FTIR) showed that Arg was successfully covalently attached to the CS. Interestingly, Arg-CS was identified as nanoparticles by atomic force microscopy (AFM) and transmission electron microscopy (TEM), whose particle size was 75.76 ± 12.07 nm based on Dynamic Light Scattering (DLS) characterization. Then, whether the prepared Arg-CS nanoparticles could encapsulate and deliver siRNA safely was investigated. Arg-CS was found to be able to encapsulate siRNAs in vitro via electrostatic interaction with siRNA; the Arg-CS/siRNA complex was safe for L1210 leukemia cells. Therefore, modification of chitosan by Arg produces novel nanoparticles to deliver siRNA into leukemia cells. This is the first time to identify Arg-CS as nanoparticles and explore their ability to deliver Rhoa siRNA into T-cell acute lymphoblastic leukemia (T-ALL) cells to advance therapies targeting Rhoa in the future. Full article

(This article belongs to the Special Issue Recent Developments and Updates in Acute Lymphoblastic Leukemia)

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Review

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20 pages, 1701 KiB

Open AccessReview

Epithelial–Mesenchymal Transition in Acute Leukemias

by Lokman Varisli and Spiros Vlahopoulos

Int. J. Mol. Sci. 2024, 25(4), 2173; https://doi.org/10.3390/ijms25042173 - 11 Feb 2024

Viewed by 1067

Abstract

Epithelial–mesenchymal transition (EMT) is a metabolic process that confers phenotypic flexibility to cells and the ability to adapt to new functions. This transition is critical during embryogenesis and is required for the differentiation of many tissues and organs. EMT can also be induced in advanced-stage cancers, leading to further malignant behavior and chemotherapy resistance, resulting in an unfavorable prognosis for patients. Although EMT was long considered and studied only in solid tumors, it has been shown to be involved in the pathogenesis of hematological malignancies, including acute leukemias. Indeed, there is increasing evidence that EMT promotes the progression of acute leukemias, leading to the emergence of a more aggressive phenotype of the disease, and also causes chemotherapy resistance. The current literature suggests that the levels and activities of EMT inducers and markers can be used to predict prognosis, and that targeting EMT in addition to conventional therapies may increase treatment success in acute leukemias. Full article

(This article belongs to the Special Issue Recent Developments and Updates in Acute Lymphoblastic Leukemia)

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21 pages, 1559 KiB

Open AccessReview

MiRNAs in Hematopoiesis and Acute Lymphoblastic Leukemia

by Diana Karen Mendiola-Soto, Diego Alberto Bárcenas-López, Carlos Jhovani Pérez-Amado, Gabriela Marisol Cruz-Miranda, Juan Manuel Mejía-Aranguré, Julian Ramírez-Bello, Alfredo Hidalgo-Miranda and Silvia Jiménez-Morales

Int. J. Mol. Sci. 2023, 24(6), 5436; https://doi.org/10.3390/ijms24065436 - 12 Mar 2023

Cited by 6 | Viewed by 2202

Abstract

Acute lymphoblastic leukemia (ALL) is the most common kind of pediatric cancer. Although the cure rates in ALL have significantly increased in developed countries, still 15–20% of patients relapse, with even higher rates in developing countries. The role of non-coding RNA genes as microRNAs (miRNAs) has gained interest from researchers in regard to improving our knowledge of the molecular mechanisms underlying ALL development, as well as identifying biomarkers with clinical relevance. Despite the wide heterogeneity reveled in miRNA studies in ALL, consistent findings give us confidence that miRNAs could be useful to discriminate between leukemia linages, immunophenotypes, molecular groups, high-risk-for-relapse groups, and poor/good responders to chemotherapy. For instance, miR-125b has been associated with prognosis and chemoresistance in ALL, miR-21 has an oncogenic role in lymphoid malignancies, and the miR-181 family can act either as a oncomiR or tumor suppressor in several hematological malignancies. However, few of these studies have explored the molecular interplay between miRNAs and their targeted genes. This review aims to state the different ways in which miRNAs could be involved in ALL and their clinical implications. Full article

(This article belongs to the Special Issue Recent Developments and Updates in Acute Lymphoblastic Leukemia)

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Graphical abstract

17 pages, 630 KiB

Open AccessReview

Pediatric Acute Lymphoblastic Leukemia Emerging Therapies—From Pathway to Target

by Anca Viorica Ivanov, Mirabela Smaranda Alecsa, Roxana Popescu, Magdalena Iuliana Starcea, Adriana Maria Mocanu, Cristina Rusu and Ingrith Crenguta Miron

Int. J. Mol. Sci. 2023, 24(5), 4661; https://doi.org/10.3390/ijms24054661 - 28 Feb 2023

Cited by 3 | Viewed by 3300

Abstract

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75–80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recognition of the importance of chromosomal abnormalities, the amplification of the oncogenes, the aberration of tumor suppressor genes, as well as the dysregulation of cellular signaling and cell cycle control. Lately, novel therapies that have already proven efficient on relapsed/refractory ALL in adults are being evaluated in clinical trials for young patients. Tirosine kinase inhibitors are, by now, part of the standardized treatment of Ph+ALL pediatric patients, and Blinatumomab, with promising results in clinical trials, received both FDA and EMA approval for use in children. Moreover, other targeted therapies such as aurora-kinase inhibitors, MEK-inhibitors, and proteasome-inhibitors are involved in clinical trials that include pediatric patients. This is an overview of the novel leukemia therapies that have been developed starting from the molecular discoveries and those that have been applied in pediatric populations. Full article

(This article belongs to the Special Issue Recent Developments and Updates in Acute Lymphoblastic Leukemia)

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