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Special Issue "Myelofibrosis and Myeloproliferative Neoplasms: Molecular Basis"

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 (30 November 2020).

Special Issue Editors

Dr. María Teresa Gómez-Casares

Guest Editor
Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas 35019, Spain
Interests: Myelofibrosis, molecular screening, next-generation sequencing, prognostic risk stratification, myeproliferative neoplasms, myeloid and hematopoeitic diseases.
Dr. Ruth Stuckey

Guest Editor
Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas 35019, Spain
Interests: Myelofibrosis, molecular screening, next-generation sequencing, prognostic risk stratification, myeproliferative neoplasms, myeloid and hematopoeitic diseases.

Special Issue Information

Dear Colleagues,

The myeloproliferative neoplasms (MPN) are a group of rare chronic disorders characterized by the clonal proliferation of one or more blood cell lines in the myeloid lineage, and include primary myelofibrosis (PMF), chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia not otherwise specified (CEL-NOS), and MPN unclassifiable (MPN-U).

As a result of increasingly economical and available next-generation sequencing technologies, genetic studies in the past decade have improved our understanding of the molecular basis of MPNs. Recent breakthroughs include the discovery of activating mutations in CSF3R in the majority of patients with CNL, the presence of a driver mutation in the JAK2, MPL or CALR genes in ET and PMF (and the JAK2V617F mutation in approximately 95% of patients with PV), as well as activating mutations of KIT in some patients with CEL-NOS. Also, some very rare cases of familial hereditary MPNs have been described, caused by inherted germline mutations.

MPNs often progress to fibrosis or acute leukemia, both associated with very poor clinical outcome. Besides defining biomarkers for diagnosis, mutational studies have revealed the prognostic relevance of many somatic mutations, helping to improve the risk stratification of patients with MPNs.

Finally, knowledge of the molecular basis of MPNs has helped identify targets for directed therapy. The constitutive activation of tyrosine kinases in hematopoietic stem cells is a common molecular basis of the MPNs, with tyrosine kinase inhibitor therapy (such as imatinib, dasatinib, ruxolitinib or midostaurin) used with varying degrees of success to treat MPN. Other molecular mechanisms have also been revealed and numerous agents in various stages of development as single or combination therapies. Despite such advancements, our understanding of the molecular pathogenesis of the MPNs – particularly CNL, CEL-NOS and MPN-U – is still insufficient and treatment options limited.

In this Special Issue we are particularly interested in original papers and review articles that address developments in our understanding of the molecular basis of myelofibrosis and the MPNs, as well as manuscripts related to the keywords listed below.

Dr. María Teresa Gómez-Casares
Dr. Ruth Stuckey
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 papers will be 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 mechanisms of disease
  • Next-generation sequencing
  • Molecular screening
  • Transformation to acute leukemia
  • Genetically-improved prognostic models
  • Fibrotic progression to fibrosis
  • Prediction of thrombotic risk
  • Germline predisposition
  • Novel targeted therapies

Published Papers (3 papers)

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Review

Open AccessReview
Emerging Role of Neutrophils in the Thrombosis of Chronic Myeloproliferative Neoplasms
Int. J. Mol. Sci. 2021, 22(3), 1143; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031143 - 24 Jan 2021
Abstract
Thrombosis is a major cause of morbimortality in patients with chronic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN). In the last decade, multiple lines of evidence support the role of leukocytes in thrombosis of MPN patients. Besides the increase in the number of cells, neutrophils [...] Read more.
Thrombosis is a major cause of morbimortality in patients with chronic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN). In the last decade, multiple lines of evidence support the role of leukocytes in thrombosis of MPN patients. Besides the increase in the number of cells, neutrophils and monocytes of MPN patients show a pro-coagulant activated phenotype. Once activated, neutrophils release structures composed of DNA, histones, and granular proteins, called extracellular neutrophil traps (NETs), which in addition to killing pathogens, provide an ideal matrix for platelet activation and coagulation mechanisms. Herein, we review the published literature related to the involvement of NETs in the pathogenesis of thrombosis in the setting of MPN; the effect that cytoreductive therapies and JAK inhibitors can have on markers of NETosis, and, finally, the novel therapeutic strategies targeting NETs to reduce the thrombotic complications in these patients. Full article
(This article belongs to the Special Issue Myelofibrosis and Myeloproliferative Neoplasms: Molecular Basis)
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Open AccessReview
Genetics and Pathogenetic Role of Inflammasomes in Philadelphia Negative Chronic Myeloproliferative Neoplasms: A Narrative Review
Int. J. Mol. Sci. 2021, 22(2), 561; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020561 - 08 Jan 2021
Abstract
The last decade has been very important for the quantity of preclinical information obtained regarding chronic myeloproliferative neoplasms (MPNs) and the following will be dedicated to the translational implications of the new biological acquisitions. The overcoming of the mechanistic model of clonal evolution [...] Read more.
The last decade has been very important for the quantity of preclinical information obtained regarding chronic myeloproliferative neoplasms (MPNs) and the following will be dedicated to the translational implications of the new biological acquisitions. The overcoming of the mechanistic model of clonal evolution and the entry of chronic inflammation and dysimmunity into the new model are the elements on which to base a part of future therapeutic strategies. The innate immune system plays a major role in this context. Protagonists of the initiation and regulation of many pathological aspects, from cytokine storms to fibrosis, the NLRP3 and AIM2 inflammasomes guide and condition the natural history of the disease. For this reason, MPNs share many biological and clinical aspects with non-neoplastic diseases, such as autoimmune disorders. Finally, cardiovascular risk and disturbances in iron metabolism and myelopoiesis are also closely linked to the role of inflammasomes. Although targeted therapies are already being tested, an increase in knowledge on the subject is desirable and potentially translates into better care for patients with MPNs. Full article
(This article belongs to the Special Issue Myelofibrosis and Myeloproliferative Neoplasms: Molecular Basis)
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Open AccessReview
The Genetic Basis of Primary Myelofibrosis and Its Clinical Relevance
Int. J. Mol. Sci. 2020, 21(23), 8885; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238885 - 24 Nov 2020
Abstract
Among classical BCR-ABL-negative myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF) is the most aggressive subtype from a clinical standpoint, posing a great challenge to clinicians. Whilst the biological consequences of the three MPN driver gene mutations (JAK2, CALR, and MPL) have [...] Read more.
Among classical BCR-ABL-negative myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF) is the most aggressive subtype from a clinical standpoint, posing a great challenge to clinicians. Whilst the biological consequences of the three MPN driver gene mutations (JAK2, CALR, and MPL) have been well described, recent data has shed light on the complex and dynamic structure of PMF, that involves competing disease subclones, sequentially acquired genomic events, mostly in genes that are recurrently mutated in several myeloid neoplasms and in clonal hematopoiesis, and biological interactions between clonal hematopoietic stem cells and abnormal bone marrow niches. These observations may contribute to explain the wide heterogeneity in patients’ clinical presentation and prognosis, and support the recent effort to include molecular information in prognostic scoring systems used for therapeutic decision-making, leading to promising clinical translation. In this review, we aim to address the topic of PMF molecular genetics, focusing on four questions: (1) what is the role of mutations on disease pathogenesis? (2) what is their impact on patients’ clinical phenotype? (3) how do we integrate gene mutations in the risk stratification process? (4) how do we take advantage of molecular genetics when it comes to treatment decisions? Full article
(This article belongs to the Special Issue Myelofibrosis and Myeloproliferative Neoplasms: Molecular Basis)
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