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Advances in Molecular Biology and Targeted Therapy of Leukemias 3.0

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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: closed (31 January 2022) | Viewed by 23846

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Special Issue Editor

Dr. Simona Soverini

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Guest Editor

Department of Experimental, Diagnostic and Specialty Medicine, Hematology/Oncology "L. e A. Seragnoli", University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
Interests: hematology; leukemias; next-generation sequencing; mutation analysis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

Over the last decade, the advent of ‘omics’ technologies has greatly improved our understanding of the molecular mechanisms underlying the initiation and progression of many forms of leukemia and has led to the identification of several “druggable” targets. The molecular dissection of the leukemia genome and transcriptome has also improved the way we diagnose, classify, and monitor patients.

This Special Issue of the International Journal of Molecular Sciences will focus on “Advances in Molecular Biology and Targeted Therapy of Leukemias”, with the aim of providing an updated overview of our current knowledge of the pathogenesis of leukemias, lymphomas, and myeloma, of the promises and pitfalls of targeted therapeutic approaches, and of how molecular profiling and molecular monitoring are being integrated into the routine management of patients.

Dr. Simona Soverini
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
lymphoma
myeloma
targeted therapy
tyrosine kinase inhibitors
minimal residual disease monitoring

Published Papers (5 papers)

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Research

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16 pages, 3291 KiB

Open AccessArticle

Antileukemic Natural Product Induced Both Apoptotic and Pyroptotic Programmed Cell Death and Differentiation Effect

by Wohn-Jenn Leu, Hsun-Shuo Chang, Ih-Sheng Chen, Jih-Hwa Guh and She-Hung Chan

Int. J. Mol. Sci. 2021, 22(20), 11239; https://doi.org/10.3390/ijms222011239 - 18 Oct 2021

Cited by 6 | Viewed by 2367

Abstract

Acute myeloid leukemia (AML) is one of the most common forms of leukemia. Despite advances in the management of such malignancies and the progress of novel therapies, unmet medical needs still exist in AML because of several factors, including poor response to chemotherapy and high relapse rates. Ardisianone, a plant-derived natural component with an alkyl benzoquinone structure, induced apoptosis in leukemic HL-60 cells. The determination of dozens of apoptosis-related proteins showed that ardisianone upregulated death receptors and downregulated the inhibitor of apoptosis protein (IAPs). Western blotting showed that ardisianone induced a dramatic increase in tumor necrosis factor receptor 2 (TNFR2) protein expression. Ardisianone also induced downstream signaling by activating caspase-8 and -3 and degradation in Bid, a caspase-8 substrate. Furthermore, ardisianone induced degradation in DNA fragmentation factor 45 kDa (DFF45), a subunit of inhibitors of caspase-activated DNase (ICAD). Q-VD-OPh (a broad-spectrum caspase inhibitor) significantly diminished ardisianone-induced apoptosis, confirming the involvement of caspase-dependent apoptosis. Moreover, ardisianone induced pyroptosis. Using transmission electron microscopic examination and Western blot analysis, key markers including gasdermin D, high mobility group box1 (HMGB1), and caspase-1 and -5 were detected. Notably, ardisianone induced the differentiation of the remaining survival cells, which were characterized by an increase in the expression of CD11b and CD68, two markers of macrophages and monocytes. Wright–Giemsa staining also showed the differentiation of cells into monocyte and macrophage morphology. In conclusion, the data suggested that ardisianone induced the apoptosis and pyroptosis of leukemic cells through downregulation of IAPs and activation of caspase pathways that caused gasdermin D cleavage and DNA double-stranded breaks and ultimately led to programmed cell death. Ardisianone also induced the differentiation of leukemic cells into monocyte-like and macrophage-like cells. The data suggested the potential of ardisianone for further antileukemic development. Full article

(This article belongs to the Special Issue Advances in Molecular Biology and Targeted Therapy of Leukemias 3.0)

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Review

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13 pages, 1244 KiB

Open AccessReview

Application of High Throughput Technologies in the Development of Acute Myeloid Leukemia Therapy: Challenges and Progress

by Wei Xiang, Yi Hui Lam, Giridharan Periyasamy and Charles Chuah

Int. J. Mol. Sci. 2022, 23(5), 2863; https://doi.org/10.3390/ijms23052863 - 05 Mar 2022

Cited by 1 | Viewed by 3791

Abstract

Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by extensive heterogeneity in genetics, response to therapy and long-term outcomes, making it a prototype example of development for personalized medicine. Given the accessibility to hematologic malignancy patient samples and recent advances in high-throughput technologies, large amounts of biological data that are clinically relevant for diagnosis, risk stratification and targeted drug development have been generated. Recent studies highlight the potential of implementing genomic-based and phenotypic-based screens in clinics to improve survival in patients with refractory AML. In this review, we will discuss successful applications as well as challenges of most up-to-date high-throughput technologies, including artificial intelligence (AI) approaches, in the development of personalized medicine for AML, and recent clinical studies for evaluating the utility of integrating genomics-guided and drug sensitivity testing-guided treatment approaches for AML patients. Full article

(This article belongs to the Special Issue Advances in Molecular Biology and Targeted Therapy of Leukemias 3.0)

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32 pages, 961 KiB

Open AccessReview

Genetic Biomarkers and Their Clinical Implications in B-Cell Acute Lymphoblastic Leukemia in Children

by Monika Lejman, Aleksandra Chałupnik, Zuzanna Chilimoniuk and Maciej Dobosz

Int. J. Mol. Sci. 2022, 23(5), 2755; https://doi.org/10.3390/ijms23052755 - 02 Mar 2022

Cited by 25 | Viewed by 9578

Abstract

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies characterized by abnormal proliferation of immature lymphoid cells. It is the most commonly diagnosed childhood cancer with an almost 80% cure rate. Despite favorable survival rates in the pediatric population, a significant number of patients develop resistance to therapy, resulting in poor prognosis. ALL is a heterogeneous disease at the genetic level, but the intensive development of sequencing in the last decade has made it possible to broaden the study of genomic changes. New technologies allow us to detect molecular changes such as point mutations or to characterize epigenetic or proteomic profiles. This process made it possible to identify new subtypes of this disease characterized by constellations of genetic alterations, including chromosome changes, sequence mutations, and DNA copy number alterations. These genetic abnormalities are used as diagnostic, prognostic and predictive biomarkers that play an important role in earlier disease detection, more accurate risk stratification, and treatment. Identification of new ALL biomarkers, and thus a greater understanding of their molecular basis, will lead to better monitoring of the course of the disease. In this article, we provide an overview of the latest information on genomic alterations found in childhood ALL and discuss their impact on patients’ clinical outcomes. Full article

(This article belongs to the Special Issue Advances in Molecular Biology and Targeted Therapy of Leukemias 3.0)

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18 pages, 2350 KiB

Open AccessReview

The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities

by Samantha Bruno, Manuela Mancini, Sara De Santis, Cecilia Monaldi, Michele Cavo and Simona Soverini

Int. J. Mol. Sci. 2021, 22(13), 6857; https://doi.org/10.3390/ijms22136857 - 25 Jun 2021

Cited by 9 | Viewed by 3680

Abstract

Acute myeloid leukemia (AML) is a hematologic malignancy caused by a wide range of alterations responsible for a high grade of heterogeneity among patients. Several studies have demonstrated that the hypoxic bone marrow microenvironment (BMM) plays a crucial role in AML pathogenesis and therapy response. This review article summarizes the current literature regarding the effects of the dynamic crosstalk between leukemic stem cells (LSCs) and hypoxic BMM. The interaction between LSCs and hypoxic BMM regulates fundamental cell fate decisions, including survival, self-renewal, and proliferation capacity as a consequence of genetic, transcriptional, and metabolic adaptation of LSCs mediated by hypoxia-inducible factors (HIFs). HIF-1α and some of their targets have been associated with poor prognosis in AML. It has been demonstrated that the hypoxic BMM creates a protective niche that mediates resistance to therapy. Therefore, we also highlight how hypoxia hallmarks might be targeted in the future to hit the leukemic population to improve AML patient outcomes. Full article

(This article belongs to the Special Issue Advances in Molecular Biology and Targeted Therapy of Leukemias 3.0)

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25 pages, 1811 KiB

Open AccessReview

Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia

by Princess D. Rodriguez, Hana Paculova, Sophie Kogut, Jessica Heath, Hilde Schjerven and Seth Frietze

Int. J. Mol. Sci. 2021, 22(5), 2683; https://doi.org/10.3390/ijms22052683 - 07 Mar 2021

Cited by 13 | Viewed by 3696

Abstract

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell acute lymphoblastic leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL. Full article

(This article belongs to the Special Issue Advances in Molecular Biology and Targeted Therapy of Leukemias 3.0)

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