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Advances in the Pathobiology, Diagnosis and Treatment of Chronic Myeloid...
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Advances in the Pathobiology, Diagnosis and Treatment of Chronic Myeloid Neoplasms

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 22646

Special Issue Editors

Dr. Luis Colomo

E-Mail Website
Guest Editor
Hematopathology Section, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain
Interests: lymphoma; immunohistochemistry; molecular biology
Dr. Xavier Calvo

E-Mail Website1 Website2
Guest Editor
Laboratori de Citologia Hematològica, Servei de Patologia, Grup de Recerca Translacional en Neoplàsies Hematològiques (GRETNHE), Hospital del Mar Research Institute (IMIM), 08003 Barcelona, Spain
Interests: hematologic malignancies diagnosis; cytomorphology; flow cytometry; myeloid neoplasms; myelodysplastic syndromes; acute myeloid leukemia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue focuses on myelodysplastic syndromes (MDS), chronic myeloproliferative neoplasms (MPN), and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). The Revised 4th Edition of the WHO Classification of Haematopoietic and Lymphoid Tissues has introduced many changes in the terminology and diagnostic approach of MDS and MDS/MPN, as well as recent knowledge regarding molecular and genetic alterations of MPN. Many questions remain unresolved and active research is ongoing in this field, and new clinicopathological entities and molecular-genetic findings have been recently described.

The purpose of this Special Issue is to offer recent studies focusing on the biology, diagnostic features, and treatment of chronic myeloid neoplasms. Original research articles and reviews are both welcome.

Dr. Luis Colomo
Dr. Xavier Calvo
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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • diagnosis
  • epigenetics
  • experimental therapeutics
  • genetics
  • chronic myeloproliferative neoplasm
  • myelodysplastic syndrome
  • molecular biology

Published Papers (5 papers)

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Research

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21 pages, 4247 KiB  
Article
Kidney Dysfunction Is Associated with Thrombosis and Disease Severity in Myeloproliferative Neoplasms: Implications from the German Study Group for MPN Bioregistry
by Judith Gecht, Ioannis Tsoukakis, Kim Kricheldorf, Frank Stegelmann, Martine Klausmann, Martin Griesshammer, Holger Schulz, Wiebke Hollburg, Joachim R. Göthert, Katja Sockel, Florian H. Heidel, Norbert Gattermann, Christoph Maintz, Haifa K. Al-Ali, Uwe Platzbecker, Richard Hansen, Mathias Hänel, Stefani Parmentier, Martin Bommer, Heike L. Pahl, Fabian Lang, Martin Kirschner, Susanne Isfort, Tim H. Brümmendorf, Konstanze Döhner and Steffen Koschmiederadd Show full author list remove Hide full author list
Cancers 2021, 13(16), 4086; https://doi.org/10.3390/cancers13164086 - 13 Aug 2021
Cited by 16 | Viewed by 3142
Abstract
Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia (ET, 33.7%), polycythemia vera [...] Read more.
Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia (ET, 33.7%), polycythemia vera (PV, 38.5%), and myelofibrosis (MF, 27.9%) were extracted from the bioregistry of the German Study Group for MPN. The total cohort was subdivided according to the calculated estimated glomerular filtration rate (eGFR, (mL/min/1.73 m2)) into eGFR1 (≥90, 21%), eGFR2 (60–89, 56%), and eGFR3 (<60, 22%). A total of 29% of the patients had a history of thrombosis. A higher rate of thrombosis and longer MPN duration was observed in eGFR3 than in eGFR2 and eGFR1. Kidney dysfunction occurred earlier in ET than in PV or MF. Multiple logistic regression analysis identified arterial hypertension, MPN treatment, increased uric acid, and lactate dehydrogenase levels as risk factors for kidney dysfunction in MPN patients. Risk factors for thrombosis included arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The risk factors for kidney dysfunction and thrombosis varied between MPN subtypes. Physicians should be aware of the increased risk for kidney disease in MPN patients, which warrants closer monitoring and, possibly, early thromboprophylaxis. Full article
(This article belongs to the Special Issue Advances in the Pathobiology, Diagnosis and Treatment of Chronic Myeloid Neoplasms)
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Review

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15 pages, 1051 KiB  
Review
New Markers of Disease Progression in Myelofibrosis
by Rita Campanelli, Margherita Massa, Vittorio Rosti and Giovanni Barosi
Cancers 2021, 13(21), 5324; https://doi.org/10.3390/cancers13215324 - 23 Oct 2021
Cited by 5 | Viewed by 4770
Abstract
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm due to the clonal proliferation of a hematopoietic stem cell. The vast majority of patients harbor a somatic gain of function mutation either of JAK2 or MPL or CALR genes in their hematopoietic cells, resulting in [...] Read more.
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm due to the clonal proliferation of a hematopoietic stem cell. The vast majority of patients harbor a somatic gain of function mutation either of JAK2 or MPL or CALR genes in their hematopoietic cells, resulting in the activation of the JAK/STAT pathway. Patients display variable clinical and laboratoristic features, including anemia, thrombocytopenia, splenomegaly, thrombotic complications, systemic symptoms, and curtailed survival due to infections, thrombo-hemorrhagic events, or progression to leukemic transformation. New drugs have been developed in the last decade for the treatment of PMF-associated symptoms; however, the only curative option is currently represented by allogeneic hematopoietic cell transplantation, which can only be offered to a small percentage of patients. Disease prognosis is based at diagnosis on the classical International Prognostic Scoring System (IPSS) and Dynamic-IPSS (during disease course), which comprehend clinical parameters; recently, new prognostic scoring systems, including genetic and molecular parameters, have been proposed as meaningful tools for a better patient stratification. Moreover, new biological markers predicting clinical evolution and patient survival have been associated with the disease. This review summarizes basic concepts of PMF pathogenesis, clinics, and therapy, focusing on classical prognostic scoring systems and new biological markers of the disease. Full article
(This article belongs to the Special Issue Advances in the Pathobiology, Diagnosis and Treatment of Chronic Myeloid Neoplasms)
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22 pages, 1543 KiB  
Review
Synoptic Diagnostics of Myeloproliferative Neoplasms: Morphology and Molecular Genetics
by Dominik Nann and Falko Fend
Cancers 2021, 13(14), 3528; https://doi.org/10.3390/cancers13143528 - 14 Jul 2021
Cited by 6 | Viewed by 3316
Abstract
The diagnosis of a myeloid neoplasm relies on a combination of clinical, morphological, immunophenotypic and genetic features, and an integrated, multimodality approach is needed for precise classification. The basic diagnostics of myeloid neoplasms still rely on cell counts and morphology of peripheral blood [...] Read more.
The diagnosis of a myeloid neoplasm relies on a combination of clinical, morphological, immunophenotypic and genetic features, and an integrated, multimodality approach is needed for precise classification. The basic diagnostics of myeloid neoplasms still rely on cell counts and morphology of peripheral blood and bone marrow aspirate, flow cytometry, cytogenetics and bone marrow trephine biopsy, but particularly in the setting of Ph− myeloproliferative neoplasms (MPN), the trephine biopsy has a crucial role. Nowadays, molecular studies are of great importance in confirming or refining a diagnosis and providing prognostic information. All myeloid neoplasms of chronic evolution included in this review, nowadays feature the presence or absence of specific genetic markers in their diagnostic criteria according to the current WHO classification, underlining the importance of molecular studies. Crucial differential diagnoses of Ph− MPN are the category of myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2, and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). This review focuses on morphological, immunophenotypical and molecular features of BCR-ABL1-negative MPN and their differential diagnoses. Furthermore, areas of difficulties and open questions in their classification are addressed, and the persistent role of morphology in the area of molecular medicine is discussed. Full article
(This article belongs to the Special Issue Advances in the Pathobiology, Diagnosis and Treatment of Chronic Myeloid Neoplasms)
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20 pages, 2484 KiB  
Review
Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms
by Laura Palomo, Pamela Acha and Francesc Solé
Cancers 2021, 13(9), 2120; https://doi.org/10.3390/cancers13092120 - 27 Apr 2021
Cited by 10 | Viewed by 3862
Abstract
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are myeloid neoplasms characterized by the presentation of overlapping features from both myelodysplastic syndromes and myeloproliferative neoplasms. Although the classification of MDS/MPN relies largely on clinical features and peripheral blood and bone marrow morphology, studies have demonstrated that a large [...] Read more.
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are myeloid neoplasms characterized by the presentation of overlapping features from both myelodysplastic syndromes and myeloproliferative neoplasms. Although the classification of MDS/MPN relies largely on clinical features and peripheral blood and bone marrow morphology, studies have demonstrated that a large proportion of patients (~90%) with this disease harbor somatic mutations in a group of genes that are common across myeloid neoplasms. These mutations play a role in the clinical heterogeneity of these diseases and their clinical evolution. Nevertheless, none of them is specific to MDS/MPN and current diagnostic criteria do not include molecular data. Even when such alterations can be helpful for differential diagnosis, they should not be used alone as proof of neoplasia because some of these mutations may also occur in healthy older people. Here, we intend to review the main genetic findings across all MDS/MPN overlap syndromes and discuss their relevance in the management of the patients. Full article
(This article belongs to the Special Issue Advances in the Pathobiology, Diagnosis and Treatment of Chronic Myeloid Neoplasms)
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28 pages, 1531 KiB  
Review
Risk-Adapted, Individualized Treatment Strategies of Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)
by Jan Philipp Bewersdorf and Amer M. Zeidan
Cancers 2021, 13(7), 1610; https://doi.org/10.3390/cancers13071610 - 31 Mar 2021
Cited by 15 | Viewed by 6762
Abstract
Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are two distinct blood cancers with a variable clinical symptom burden and risk of progression to acute myeloid leukemia. Management decisions should be guided by individual patient and disease characteristics and based on validated risk [...] Read more.
Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are two distinct blood cancers with a variable clinical symptom burden and risk of progression to acute myeloid leukemia. Management decisions should be guided by individual patient and disease characteristics and based on validated risk stratification tools. While supportive care with red blood cell transfusions, erythropoiesis-stimulating agents, and iron chelation remains the mainstay of therapy for lower-risk (LR)-MDS patients, luspatercept has recently been approved for transfusion-dependent anemic LR-MDS patients ending a decade without any new drug approvals for MDS. For higher-risk patients, allogeneic hematopoietic cell transplant (allo-HCT) remains the only curative therapy for both MDS and CMML but most patients are not eligible for allo-HCT. For those patients, the hypomethylating agents (HMA) azacitidine and decitabine remain standard of care with azacitidine being the only agent that has shown an overall survival benefit in randomized trials. Although early results from novel molecularly driven agents such as IDH1/2 inhibitors, venetoclax, magrolimab, and APR-246 for MDS as well as tagraxofusp, tipifarnib, and lenzilumab for CMML appear encouraging, confirmatory randomized trials must be completed to fully assess their safety and efficacy prior to routine clinical use. Herein, we review the current management of MDS and CMML and conclude with a critical appraisal of novel therapies and general trends in this field. Full article
(This article belongs to the Special Issue Advances in the Pathobiology, Diagnosis and Treatment of Chronic Myeloid Neoplasms)
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