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Thrombosis Research Oct 2022Splanchnic vein thrombosis (SVT) in the setting of myeloproliferative neoplasm (MPN) is a unique clinical entity that requires close interdisciplinary coordination for... (Review)
Review
Splanchnic vein thrombosis (SVT) in the setting of myeloproliferative neoplasm (MPN) is a unique clinical entity that requires close interdisciplinary coordination for proper diagnosis and management. The pathobiology of MPN-SVT is not fully understood, but recent developments have revealed the central role of endothelial cells. In this multidisciplinary review, we summarize the epidemiology of MPN-SVT and then critically evaluate the pathogenic features of this complication, with a focus on endothelial cell biology. We then discuss diagnostic considerations, including imaging modalities and MPN-specific investigations. Finally, we critically review the evidence supporting clinical management of MPN-SVT, including anticoagulation, interventional radiology procedures, MPN-related therapies, and liver transplantation. We conclude that further studies are needed to improve our understanding of MPN-SVT and the outcomes of patients with this debilitating complication.
Topics: Anticoagulants; Endothelial Cells; Humans; Myeloproliferative Disorders; Neoplasms; Splanchnic Circulation; Venous Thrombosis
PubMed: 35963121
DOI: 10.1016/j.thromres.2022.08.003 -
American Journal of Clinical Pathology Apr 2022Primary myelofibrosis (PMF) is a BCR/ABL1-negative myeloproliferative neoplasm (MPN) with a shorter overall survival and a higher leukemic transformation than other...
OBJECTIVES
Primary myelofibrosis (PMF) is a BCR/ABL1-negative myeloproliferative neoplasm (MPN) with a shorter overall survival and a higher leukemic transformation than other BCR/ABL1-negative MPNs. Diagnosis of PMF can be challenging given its clinical, morphologic, molecular overlap with other myeloid neoplasms also associated with myelofibrosis, and reactive conditions.
METHODS
We summarize and discuss the clinical, morphologic, and molecular features useful for diagnosing PMF as well as salient features helpful in distinguishing PMF from myelodysplastic syndrome with associated fibrosis and autoimmune myelofibrosis using a case-based approach.
RESULTS
PMF in both its prefibrotic and fibrotic stages, the latter characterized by reticulin/collagen marrow fibrosis, is characterized by a proliferation of predominantly abnormal megakaryocytes and granulocytes in the bone marrow. Driver mutations in JAK2, CALR, or MPLare seen in approximately 90% of PMF cases. In triple-negative cases, the presence of cytogenetic abnormalities and other somatic mutations identified by next-generation sequencing can help establish a diagnosis of PMF in the appropriate clinical and morphologic context.
CONCLUSIONS
Given the significant difference in prognosis and treatment, integration of clinical, morphological, and molecular/genetic findings is essential in distinguishing PMF from other etiologies that can demonstrate myelofibrosis.
Topics: Bone Marrow; Calreticulin; Humans; Janus Kinase 2; Megakaryocytes; Mutation; Myeloproliferative Disorders; Primary Myelofibrosis; Prognosis
PubMed: 35238345
DOI: 10.1093/ajcp/aqac016 -
Blood Reviews Jul 2020The management of myelofibrosis (MF) is predominantly supportive, with the use of JAK2 inhibitors or allogeneic stem cell transplantation reserved for patients predicted... (Review)
Review
The management of myelofibrosis (MF) is predominantly supportive, with the use of JAK2 inhibitors or allogeneic stem cell transplantation reserved for patients predicted to have poor overall survival. Identification of these patients is aided by a number of prognostic scoring systems, foremost among them the Dynamic International Prognostic Scoring System (DIPSS). Similarly, the use of cytoreductive therapies in essential thrombocytosis (ET) and polycythemia vera (PV) is targeted to patients identified as at highest risk of thrombosis. In this context, age and history of prior thrombosis are the strongest risk factors. Several studies have sought to improve the accuracy of prognostic modelling by encorporating a wider range of clinical and genomic variables, while also assessing those predictive for other endpoints, such as disease transformation. This review aims to summarise and evaluate existing prognostic models in the myeloproliferative neoplasms, and examine ways in which they can be further refined.
Topics: Animals; Cytogenetic Analysis; Disease Management; Humans; Models, Biological; Mutation; Myeloproliferative Disorders; Prognosis
PubMed: 32532453
DOI: 10.1016/j.blre.2020.100713 -
Seminars in Diagnostic Pathology Nov 2020Myeloid diseases detected as primary or secondary lesions in the lung and pleura are rare. Clinical presentations and radiographic results may vary significantly... (Review)
Review
Myeloid diseases detected as primary or secondary lesions in the lung and pleura are rare. Clinical presentations and radiographic results may vary significantly depending on the nature of the diseases. The most common diseases associated with lung and pleura involvement are myeloid sarcoma/acute myeloid leukemia (AML) and extramedullary hematopoiesis (EMH). AML typically represents localized involvement by systemic acute leukemia, while EMH is frequently secondary to underlying benign hematolymphoid disorders or myeloproliferative neoplasms. This review provides an overview of the pathogenesis, clinical presentations, radiologic/imaging studies, pathologic and genetic findings, and treatment/outcomes associated with myeloid diseases in the lung and pleura.
Topics: Diagnosis, Differential; Genetic Predisposition to Disease; Hematopoiesis, Extramedullary; Humans; Leukemia, Myeloid, Acute; Lung; Myeloproliferative Disorders; Pathology, Molecular; Pleura; Sarcoma, Myeloid; Thalassemia; Treatment Outcome
PubMed: 32591154
DOI: 10.1053/j.semdp.2020.06.002 -
Haematologica May 2020The bone marrow niche is a complex and dynamic structure composed of a multitude of cell types which functionally create an interactive network facilitating... (Review)
Review
The bone marrow niche is a complex and dynamic structure composed of a multitude of cell types which functionally create an interactive network facilitating hematopoietic stem cell development and maintenance. Its specific role in the pathogenesis, response to therapy, and transformation of myeloproliferative neoplasms has only recently been explored. Niche functionality is likely affected not only by the genomic background of the myeloproliferative neoplasm-associated mutated hematopoietic stem cells, but also by disease-associated 'chronic inflammation', and subsequent adaptive and innate immune responses. 'Cross-talk' between mutated hematopoietic stem cells and multiple niche components may contribute to propagating disease progression and mediating drug resistance. In this timely article, we will review current knowledge surrounding the deregulated bone marrow niche in myeloproliferative neoplasms and suggest how this may be targeted, either directly or indirectly, potentially influencing therapeutic choices both now and in the future.
Topics: Bone Marrow; Hematopoietic Stem Cells; Humans; Myeloproliferative Disorders; Neoplasms; Stem Cell Niche
PubMed: 32241851
DOI: 10.3324/haematol.2019.243121 -
International Review of Cell and... 2022Molecular laboratory investigations for myeloproliferative neoplasm (MPN) can ideally be divided into two distincts groups, those for the detection of the BCR-ABL...
Molecular laboratory investigations for myeloproliferative neoplasm (MPN) can ideally be divided into two distincts groups, those for the detection of the BCR-ABL rearrangement (suspect of chronic myeloid leukemia) and those for the variants determination of the driver genes of the negative Philadelphia forms (MPN Ph neg). The BCR-ABL detection is based on RT-Polymerase Chain Reaction techniques and more recently on droplet digital PCR (ddPCR). For this type of analysis, combined with chromosome banding analysis (CBA) and Fluorescent in situ hybridization (FISH), it is essential to quantify BCR-ABL mutated copies by standard curve method. The investigation on driver genes for MPN Ph neg forms includes activity for erythroid forms such as Polycythemia Vera (test JAK2V617F and JAK2 exon 12), for non-erythroid forms such as essential thrombocythemia and myelofibrosis (test JAK2V617F, CALR exon 9, MPL exon 10), for "atypical" ones such as mastocytosis (cKIT D816V test) and for hypereosinophilic syndrome (FIP1L1-PDGFRalpha test). It's crucial to assign prognosis value through calculating allelic burden of JAK2 V617F variant and determining CALR esone 9 variants (type1/1like, type2/2like and atypical ones). A fundamental innovation for investigating triple negative cases for JAK2, CALR, MPL and for providing prognostic score is the use of Next Generation Sequencing panels containing high molecular risk genes as ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2. This technique allows to detect additional or subclonal mutations which are usually acquired in varying sized sub-clones of hematopoietic progenitors. These additional variants have a prognostic significance and should be indagated to exclude false negative cases.
Topics: Calreticulin; Humans; In Situ Hybridization, Fluorescence; Mutation; Myeloproliferative Disorders; Receptors, Thrombopoietin; Thrombocythemia, Essential; Transcription Factors
PubMed: 35153004
DOI: 10.1016/bs.ircmb.2021.02.010 -
Expert Opinion on Drug Safety Dec 2021: Hydroxyurea (HU) is an S-phase specific oral chemotherapeutic agent that inhibits ribonucleotide diphosphate reductase. It is the most common used cytoreductive drug... (Review)
Review
: Hydroxyurea (HU) is an S-phase specific oral chemotherapeutic agent that inhibits ribonucleotide diphosphate reductase. It is the most common used cytoreductive drug in patients (pts) with negative myeloproliferative neoplasms (MPN) and sickle cell disease (SCD). The World Health Organization lists HU as an "essential drug". Although most patients tolerate HU well, cutaneous adverse events (CAE) are frequent side effects and may limit its long-term use. This has become increasingly evident in recent years, especially in MPN patients, where CAE were previously underestimated and underdiagnosed.: In this review, we present the available literature on HU-related CAE in MPN patients. In particular, data from a recently published and so far, only prospective non-interventional study investigating CAE in 172 MPN patients will be discussed in detail and compared with previously available data. Finally, we give an overview of the management of HU-related CAE in MPN patients and provide recommendations on the practical clinical approach.: In clinical practice, HU associated CAE are common and have important diagnostic and therapeutic consequences. Therefore, they should be considered in all MPN patients treated with HU in the future.
Topics: Anemia, Sickle Cell; Antineoplastic Agents; Humans; Hydroxyurea; Myeloproliferative Disorders; Skin Diseases
PubMed: 34181494
DOI: 10.1080/14740338.2021.1945032 -
American Journal of Hematology Apr 2023
Topics: Humans; Blast Crisis; Myeloproliferative Disorders; Hematopoietic Stem Cell Transplantation
PubMed: 36655312
DOI: 10.1002/ajh.26849 -
Best Practice & Research. Clinical... Jun 2022Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders commonly diagnosed in the seventh decade of life. With increasing access to blood surveillance, the... (Review)
Review
Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders commonly diagnosed in the seventh decade of life. With increasing access to blood surveillance, the number of adolescent and young adults (AYAs) diagnosed with MPNs is increasing. AYAs represent a unique cohort of MPN patients with differing challenges and psychosocial needs. The majority of AYA patients are females diagnosed with essential thrombocythaemia and most are asymptomatic at diagnosis. There is a striking predisposition to venous thrombotic events with a significant number experiencing splanchnic venous thrombosis (up to 70% of venous events). When compared to older patients, AYAs appear to have an indolent disease course. Interferon is the preferred cytoreductive agent in this population; indications for commencing treatment mirror those of older adults and are determined by the presence of high-risk features for thromboembolic events.
Topics: Female; Humans; Young Adult; Adolescent; Aged; Male; Neoplasms; Myeloproliferative Disorders; Thrombocythemia, Essential; Thrombosis; Disease Progression
PubMed: 36333071
DOI: 10.1016/j.beha.2022.101374 -
International Journal of Molecular... Mar 2021mutations are a revolutionary discovery and represent an important hallmark of myeloproliferative neoplasms (MPN), especially essential thrombocythemia and primary... (Review)
Review
mutations are a revolutionary discovery and represent an important hallmark of myeloproliferative neoplasms (MPN), especially essential thrombocythemia and primary myelofibrosis. To date, several mutations were identified, with only frameshift mutations linked to the diseased phenotype. It is of diagnostic and prognostic importance to properly define the type of mutation and subclassify it according to its structural similarities to the classical mutations, a 52-bp deletion (type 1 mutation) and a 5-bp insertion (type 2 mutation), using a statistical approximation algorithm (AGADIR). Today, the knowledge on the pathogenesis of -positive MPN is expanding and several cellular mechanisms have been recognized that finally cause a clonal hematopoietic expansion. In this review, we discuss the current basis of the cellular effects of mutants and the understanding of its implementation in the current diagnostic laboratorial and medical practice. Different methods of detection are explained and a diagnostic algorithm is shown that aids in the approach to -positive MPN. Finally, contemporary methods joining artificial intelligence in accordance with molecular-genetic biomarkers in the approach to MPN are presented.
Topics: Algorithms; Animals; Artificial Intelligence; Biomarkers; Calreticulin; DNA Mutational Analysis; Gene Deletion; Hematology; Humans; Ligands; Machine Learning; Molecular Chaperones; Mutation; Myeloproliferative Disorders; Phenotype; Prognosis; Signal Transduction; Thrombocytosis
PubMed: 33806036
DOI: 10.3390/ijms22073371