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Molecular Research on Myeloproliferative Disorders
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Molecular Research on Myeloproliferative Disorders

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 August 2023) | Viewed by 10203

Special Issue Editors

Prof. Dr. Anna Rita Migliaccio

E-Mail Website
Guest Editor
1. Università Campus Bio-Medico di Roma Via Alvaro del Portillo, 21 00128 Roma, Italy
2. Altius Institute for Biomedical Sciences, Seattle, WA 98121, USA
Interests: experimental hematology; hematopoietic stem cells; microenvironment; erythropoiesis; myeloproliferative neoplasms
Prof. Dr. Ronald Hoffman

E-Mail Website
Guest Editor
Tisch Cancer Institute Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1079, New York, NY 10029, USA
Interests: hematopoietic stem cells; megakaryocytes; myeloproliferative neoplasms; bone marrow microenvironment; hematopoietic stem cells and other cells generated in vitro for therapy

Special Issue Information

Dear Colleagues, 

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are chronic hematological malignancies which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Polycythemia vera and essential thrombocythemia are associated with increased numbers of myeloid cells including red cells, white blood cells and platelets with one lineage predominating depending on the individual disease. Polycythemia vera and essential thrombocythemia, however, are capable of clonal evolution and clinical progression over a decade or two to myelofibrosis, a state very similar to that of primary myelofibrosis, with ineffective hematopoiesis and fibrosis in the bone marrow and associated with a profound pro-inflammatory milieu. Myelofibrosis and primary myelofibrosis have disabling systemic symptoms, such as weight loss, early satiety, bone pain, and fevers, and present circulating malignant hematopoietic stem cells (HSC) which establish extramedullary hematopoiesis in sites such as the spleen. Over 50% of these patients eventually develop a form of acute leukemia termed MPN-blast crisis which is associated with an overall survival of <10 months. Recent progresses in our understanding of the landscape of genetic lesions associated with MPNs and advances in the power of the diagnostic tools are providing unprecedented opportunities to improve the prognosis and risk stratification and to develop personalized therapies for this class of disorders, some of which, such as primary myelofibrosis and its blast-crisis, are still an unmet clinical need. Authors are invited to submit original research and review articles which address the progress and current standing of the pathobiological pathways leading to MPNs.

Topics include, but are not limited to:

  • Identification of novel genetic lesions.
  • Insights provided by the genetic lesions on prognosis, risk stratification and personalized therapies.
  • Hematopoietic stem cell abnormalities that may be exploited for therapy.
  • Abnormalities in the interactions between the malignant HSC and their supportive microenvironment which drive disease progression.
  • Role of the progeny (megakaryocytes, neutrophils, macrophages, and mast cells) of the malignant HSC in shaping the malignant HSC supportive microenvironment.
  • The inflammosome and disease progression
  • Advances is the diagnostic tools (Imaging, single cell sequencing, multi-plex single cell cytokine profiling, machine deep learning).
  • Novel animal models.

Prof. Dr. Anna Rita Migliaccio
Prof. Dr. Ronald Hoffman
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

  • Philadelphia chromosome-negative myeloproliferative neoplasms
  • driver mutations
  • pathobiological mechanisms
  • disease interventions and biomarkers

Published Papers (5 papers)

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Research

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9 pages, 854 KiB  
Communication
Conventional Cytogenetic Analysis and Array CGH + SNP Identify Essential Thrombocythemia and Prefibrotic Primary Myelofibrosis Patients Who Are at Risk for Disease Progression
by Joseph Tripodi, Ronald Hoffman, Douglas Tremblay, Daiva Ahire, John Mascarenhas, Marina Kremyanskaya and Vesna Najfeld
Int. J. Mol. Sci. 2024, 25(7), 4061; https://doi.org/10.3390/ijms25074061 - 5 Apr 2024
Viewed by 3289
Abstract
The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and [...] Read more.
The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH + SNP) in patients with ET or prePMF to determine whether the combined analysis of both methodologies can identify patients who may be at a higher risk of disease progression. We performed a comprehensive genomic review on 169 patients with a clinical diagnosis of ET (154 patients) or prePMF (15 patients). Genomic alterations detected by CC or array-CGH + SNP were detected in 36% of patients. In patients who progressed, 68% had an abnormal genomic finding by either technology. There was a shorter progression-free survival (PFS) among patients who were cytogenetically abnormal or who were cytogenetically normal but had an abnormal aCGH + SNP result. Leveraging the ability to detect submicroscopic copy number alterations and regions of copy neutral-loss of heterozygosity, we identified a higher number of patients harboring genomic abnormalities than previously reported. These results underscore the importance of genomic analysis in prognostication and provide valuable information for clinical management and treatment decisions. Full article
(This article belongs to the Special Issue Molecular Research on Myeloproliferative Disorders)
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16 pages, 2643 KiB  
Article
Mutation-Driven S100A8 Overexpression Confers Aberrant Phenotypes in Type 1 CALR-Mutated MPN
by Ying-Hsuan Wang, Ying-Ju Chen, Yi-Hua Lai, Ming-Chung Wang, Yi-Yang Chen, Yu-Ying Wu, Yao-Ren Yang, Hsing-Yi Tsou, Chian-Pei Li, Chia-Chen Hsu, Cih-En Huang and Chih-Cheng Chen
Int. J. Mol. Sci. 2023, 24(10), 8747; https://doi.org/10.3390/ijms24108747 - 14 May 2023
Cited by 2 | Viewed by 1863
Abstract
Numerous pathogenic CALR exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion; CALRDEL) and type 2 (5bp insertion; CALRINS) being the most prevalent. Despite the universal pathobiology of MPN driven by various CALR [...] Read more.
Numerous pathogenic CALR exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion; CALRDEL) and type 2 (5bp insertion; CALRINS) being the most prevalent. Despite the universal pathobiology of MPN driven by various CALR mutants, it is unclear why different CALR mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in CALRDEL but not in CALRINS MPN-model cells. The expression of S100a8 could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting S100a8 promoter region in CALRDEL cells as compared to CALRINS cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in CALRDEL cells. Clinical validation showed significantly enhanced S100A8 expression in CALRDEL-mutated MPN patients compared to CALRINS-mutated cases, and thrombocytosis was less prominent in those with S100A8 upregulation. This study provides indispensable insights into how different CALR mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN. Full article
(This article belongs to the Special Issue Molecular Research on Myeloproliferative Disorders)
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Review

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14 pages, 1125 KiB  
Review
Exploring the Molecular Aspects of Myeloproliferative Neoplasms Associated with Unusual Site Vein Thrombosis: Review of the Literature and Latest Insights
by Erika Morsia, Elena Torre, Francesco Martini, Sonia Morè, Antonella Poloni, Attilio Olivieri and Serena Rupoli
Int. J. Mol. Sci. 2024, 25(3), 1524; https://doi.org/10.3390/ijms25031524 - 26 Jan 2024
Cited by 2 | Viewed by 1251
Abstract
Myeloproliferative neoplasms (MPNs) are the leading causes of unusual site thrombosis, affecting nearly 40% of individuals with conditions like Budd–Chiari syndrome or portal vein thrombosis. Diagnosing MPNs in these cases is challenging because common indicators, such as spleen enlargement and elevated blood cell [...] Read more.
Myeloproliferative neoplasms (MPNs) are the leading causes of unusual site thrombosis, affecting nearly 40% of individuals with conditions like Budd–Chiari syndrome or portal vein thrombosis. Diagnosing MPNs in these cases is challenging because common indicators, such as spleen enlargement and elevated blood cell counts, can be obscured by portal hypertension or bleeding issues. Recent advancements in diagnostic tools have enhanced the accuracy of MPN diagnosis and classification. While bone marrow biopsies remain significant diagnostic criteria, molecular markers now play a pivotal role in both diagnosis and prognosis assessment. Hence, it is essential to initiate the diagnostic process for splanchnic vein thrombosis with a JAK2 V617F mutation screening, but a comprehensive approach is necessary. A multidisciplinary strategy is vital to accurately determine the specific subtype of MPNs, recommend additional tests, and propose the most effective treatment plan. Establishing specialized care pathways for patients with splanchnic vein thrombosis and underlying MPNs is crucial to tailor management approaches that reduce the risk of hematological outcomes and hepatic complications. Full article
(This article belongs to the Special Issue Molecular Research on Myeloproliferative Disorders)
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16 pages, 1234 KiB  
Review
Myeloproliferative Neoplasms: Contemporary Review and Molecular Landscape
by Muftah Mahmud, Swati Vasireddy, Krisstina Gowin and Akshay Amaraneni
Int. J. Mol. Sci. 2023, 24(24), 17383; https://doi.org/10.3390/ijms242417383 - 12 Dec 2023
Viewed by 1616
Abstract
Myelofibrosis (MF), Myeloproliferative neoplasms (MPNs), and MDS/MPN overlap syndromes have a broad range of clinical presentations and molecular abnormalities, making their diagnosis and classification complex. This paper reviews molecular aberration, epigenetic modifications, chromosomal anomalies, and their interactions with cellular and other immune mechanisms [...] Read more.
Myelofibrosis (MF), Myeloproliferative neoplasms (MPNs), and MDS/MPN overlap syndromes have a broad range of clinical presentations and molecular abnormalities, making their diagnosis and classification complex. This paper reviews molecular aberration, epigenetic modifications, chromosomal anomalies, and their interactions with cellular and other immune mechanisms in the manifestations of these disease spectra, clinical features, classification, and treatment modalities. The advent of new-generation sequencing has broadened the understanding of the genetic factors involved. However, while great strides have been made in the pharmacological treatment of these diseases, treatment of advanced disease remains hematopoietic stem cell transplant. Full article
(This article belongs to the Special Issue Molecular Research on Myeloproliferative Disorders)
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14 pages, 1388 KiB  
Review
Diagnosis- and Prognosis-Related Gene Alterations in BCR::ABL1-Negative Myeloproliferative Neoplasms
by Soji Morishita and Norio Komatsu
Int. J. Mol. Sci. 2023, 24(16), 13008; https://doi.org/10.3390/ijms241613008 - 21 Aug 2023
Viewed by 1487
Abstract
BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are a group of hematopoietic malignancies in which somatic mutations are acquired in hematopoietic stem/progenitor cells, resulting in an abnormal increase in blood cells in peripheral blood and fibrosis in bone marrow. Mutations in JAK2, MPL, [...] Read more.
BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are a group of hematopoietic malignancies in which somatic mutations are acquired in hematopoietic stem/progenitor cells, resulting in an abnormal increase in blood cells in peripheral blood and fibrosis in bone marrow. Mutations in JAK2, MPL, and CALR are frequently found in BCR::ABL1-negative MPNs, and detecting typical mutations in these three genes has become essential for the diagnosis of BCR::ABL1-negative MPNs. Furthermore, comprehensive gene mutation and expression analyses performed using massively parallel sequencing have identified gene mutations associated with the prognosis of BCR::ABL1-negative MPNs such as ASXL1, EZH2, IDH1/2, SRSF2, and U2AF1. Furthermore, single-cell analyses have partially elucidated the effect of the order of mutation acquisition on the phenotype of BCR::ABL1-negative MPNs and the mechanism of the pathogenesis of BCR::ABL1-negative MPNs. Recently, specific CREB3L1 overexpression has been identified in megakaryocytes and platelets in BCR::ABL1-negative MPNs, which may be promising for the development of diagnostic applications. In this review, we describe the genetic mutations found in BCR::ABL1-negative MPNs, including the results of analyses conducted by our group. Full article
(This article belongs to the Special Issue Molecular Research on Myeloproliferative Disorders)
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