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Molecular Markers and Targets in Acute Myeloid 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: closed (31 July 2023) | Viewed by 10801

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Special Issue Editor

Dr. Francesco Pallotti

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Guest Editor

1. Department of Medicine and Surgery, Clinical Biochemistry and Clinical Molecular Biology, Università degli Studi dell'Insubria, Varese, Italy
2. SMEL Genetics-SSD Cytogenetics and Medical Genetics, Ospedale Macchi-ASST Settelaghi, Viale Borri 57, 21100 Varese, Italy
Interests: mitochondrial DNA; mitochondrial disorders; myeloproliferative neoplasms; inherited thrombophilias; nonsyndromic hearing loss; pharmacogenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is devoted to the diagnostic and therapeutic role of molecular markers in acute myeloid leukemia. Acute myeloid leukemia (AML) is a heterogeneous hematologic neoplasm in terms of clinical features, underlying pathogenesis, and treatment outcomes. The continuous accumulation of genetic data due to improved molecular techniques leads us to reconsider the role of these mutations in the development of the disease, and to shed light on the possible role of these mutations as therapeutic targets for biological drug development. Recent advances in genomic techniques have unveiled the molecular complexity of AML leukemogenesis, which in turn has led to refinements in risk stratification and personalized therapeutic strategies for AML patients. Incorporating prognostic and druggable genetic biomarkers into clinical practice to guide patient-specific treatment will be the cornerstone of AML therapy. This Special Issue will compile new data and concepts regarding the leukemogenic role and hierarchical definition of driver mutations to better understand the molecular and pathophysiological functions of key genes that exert leukemogenic potential, which is essential to translate these findings into improved treatment for AML.

Dr. Francesco Pallotti
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 myeloid leukemia
myeloproliferative neoplasms
myelodysplastic syndromes
genetic markers
risk stratification
therapeutic target

Published Papers (3 papers)

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Research

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16 pages, 3330 KiB

Open AccessArticle

Dysregulation of SIRT3 SUMOylation Confers AML Chemoresistance via Controlling HES1-Dependent Fatty Acid Oxidation

by Yirong Zhang, Yajie Shen, Weiqing Wei, Wenhan Wang, Daiji Jiang, Yizhuo Ren, Zijing Peng, Qiuju Fan, Jinke Cheng and Jiao Ma

Int. J. Mol. Sci. 2022, 23(15), 8282; https://doi.org/10.3390/ijms23158282 - 27 Jul 2022

Cited by 8 | Viewed by 2346

Abstract

Sirtuin 3 (SIRT3) deacetylase is a key regulator for chemoresistance in acute myeloid leukemia (AML) cells due to its capability of modulating mitochondrial metabolism and reactive oxygen species (ROS). SIRT3 is de-SUMOylated by SUMO-specific peptidase 1 (SENP1), which enhances its deacetylase activity. Therefore, dysregulation of SIRT3 SUMOylation may lead to fortified chemoresistance in AML. Indeed, SIRT3 de-SUMOylation was induced by chemotherapeutic agents, which in turn, exacerbated resistance against chemotherapies in AML by activating SIRT3 via preventing its proteasome degradation. Furthermore, RNA-seq revealed that expression of a collection of genes was altered by SIRT3 de-SUMOylation including inhibition of transcription factor Hes Family BHLH Transcription Factor 1 (HES1), a downstream substrate of Notch1 signaling pathway, leading to increased fatty acids oxidation (FAO). Moreover, the SENP1 inhibitor momordin-Ic or HES1 overexpression synergized with cytarabine to eradicate AML cells in vitro and in xenograft mouse models. In summary, the current study revealed a novel role of SIRT3 SUMOylation in the regulation of chemoresistance in AML via HES1-dependent FAO and provided a rationale for SIRT3 SUMOylation and FAO targeted interventions to improve chemotherapies in AML. Full article

(This article belongs to the Special Issue Molecular Markers and Targets in Acute Myeloid Leukemia)

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Review

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14 pages, 317 KiB

Open AccessReview

Role of Biomarkers in the Management of Acute Myeloid Leukemia

by Sara Small, Timothy S. Oh and Leonidas C. Platanias

Int. J. Mol. Sci. 2022, 23(23), 14543; https://doi.org/10.3390/ijms232314543 - 22 Nov 2022

Cited by 4 | Viewed by 2553

Abstract

Despite many recent advances in treatment options, acute myeloid leukemia (AML) still has a high mortality rate. One important issue in optimizing outcomes for AML patients lies in the limited ability to predict response to specific therapies, duration of response, and likelihood of relapse. With evolving genetic characterization and improving molecular definitions, the ability to predict outcomes and long-term prognosis is slowly improving. The majority of the currently used prognostic assessments relate to molecular and chromosomal abnormalities, as well as response to initial therapy. These risk categories, however, do not account for a large amount of the variability in AML. Laboratory techniques now utilized in the clinic extend beyond bone marrow morphology and single gene sequencing, to next-generation sequencing of large gene panels and multiparameter flow cytometry, among others. Other technologic advances, such as gene expression analysis, have yet to demonstrate enough predictive and prognostic power to be employed in clinical medicine outside of clinical trials, but may be incorporated into the clinic in the future. In this review, we discuss the utility of current biomarkers, and present novel biomarker techniques and strategies that are in development for AML patients. Measurable residual disease (MRD) is a powerful prognostic tool that is increasingly being incorporated into clinical practice, and there are some exciting emerging biomarker technologies that have the potential to improve prognostic power in AML. As AML continues to be a difficult-to-treat disease with poor outcomes in many subtypes, advances in biomarkers that lead to better treatment decisions are greatly needed. Full article

(This article belongs to the Special Issue Molecular Markers and Targets in Acute Myeloid Leukemia)

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14 pages, 1844 KiB

Open AccessReview

Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia

by Seiichiro Katagiri, SungGi Chi, Yosuke Minami, Kentaro Fukushima, Hirohiko Shibayama, Naoko Hosono, Takahiro Yamauchi, Takanobu Morishita, Takeshi Kondo, Masamitsu Yanada, Kazuhito Yamamoto, Junya Kuroda, Kensuke Usuki, Daigo Akahane and Akihiko Gotoh

Int. J. Mol. Sci. 2022, 23(9), 4694; https://doi.org/10.3390/ijms23094694 - 23 Apr 2022

Cited by 9 | Viewed by 4805

Abstract

KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting KIT mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients’ prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of KIT mutations in AML, (2) the data in AML with KIT mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting KIT mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML. Full article

(This article belongs to the Special Issue Molecular Markers and Targets in Acute Myeloid Leukemia)

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