2,498 results match your criteria Mastocytosis Systemic


New Insights into the Pathogenesis of Systemic Mastocytosis.

Authors:
Zhixiong Li

Int J Mol Sci 2021 May 5;22(9). Epub 2021 May 5.

Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany.

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the D816V mutation. Read More

View Article and Full-Text PDF

Clinical and histopathological features of myeloid neoplasms with concurrent Janus kinase 2 (JAK2) V617F and KIT proto-oncogene, receptor tyrosine kinase (KIT) D816V mutations.

Br J Haematol 2021 Jun 1. Epub 2021 Jun 1.

Haematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

We report on 45 patients with myeloid neoplasms and concurrent Janus kinase 2 (JAK2) V617F and KIT proto-oncogene, receptor tyrosine kinase (KIT) D816V (JAK2 /KIT ) mutations, which are individually identified in >60% of patients with classical myeloproliferative neoplasms (MPN) and >90% of patients with systemic mastocytosis (SM) respectively. In SM, the concurrent presence of a clonal non-mast cell neoplasm [SM with associated haematological neoplasm (SM-AHN)] usually constitutes a distinct subtype associated with poor survival. All 45 patients presented with a heterogeneous combination of clinical/morphological features typical of the individual disorders (e. Read More

View Article and Full-Text PDF

Divergent PGD and leukotriene C metabolite excretion following aspirin therapy: Ten patients with systemic mastocytosis.

Prostaglandins Other Lipid Mediat 2021 Aug 21;155:106563. Epub 2021 May 21.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.

Aspirin-exacerbated respiratory disease and some cases of chronic idiopathic urticaria are disorders in which increased baseline urinary excretion of leukotriene(LT)E4 further increases following aspirin administration. Increased urinary excretion of the metabolites of prostaglandin D2, 11β-prostaglandin(PG)F2α and (2,3-dinor)-11β-PGF2α, have been documented in systemic mastocytosis (SM) and in mast cell activation syndrome (MCAS). Symptoms due to increased baseline and/or episodic release of PGD2 can be prevented with aspirin, an inhibitor of cyclooxygenase (COX)1 and COX2. Read More

View Article and Full-Text PDF

Psychometric evaluation of the Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF).

Leuk Res 2021 May 1;108:106606. Epub 2021 May 1.

Stanford University Medical Center, Palo Alto, CA, USA.

Background: The Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF) was developed to evaluate symptoms of advanced systemic mastocytosis (AdvSM). This study aimed to psychometrically evaluate AdvSM-SAF scores and provide score interpretation guidelines.

Methods: The 10-item AdvSM-SAF was administered daily (scored as a seven-day average) in EXPLORER, an open-label Phase 1 study in AdvSM. Read More

View Article and Full-Text PDF

Clinical and Demographic Characteristics of Cutaneous Mastocytosis in Childhood: Single-center Experience.

J Pediatr Hematol Oncol 2021 May 18. Epub 2021 May 18.

Departments of Pediatric Hematology and Oncology Pediatric Allergy and Immunology, Ankara City Hospital, Children's Hospital Department of Pediatric Hematology and Oncology, Ankara Atilim University Department of Genetics, Ankara City Hospital, Ankara, Turkey.

Introduction: Mastocytosis is a rare and heterogenous disease, and in children it is generally limited to the skin and tends to regress spontaneously in adolescence.

Aim: In this study, demographic, clinical, and laboratory characteristics of pediatric patients with mastocytosis, and also coexisting diseases were investigated.

Results: A total of 61 pediatric patients were included in the study. Read More

View Article and Full-Text PDF

GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness.

Blood 2021 May 11. Epub 2021 May 11.

Centre de Recherche en Cancérologie de Marseille - Inserm U1068, CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France.

Systemic mastocytosis (SM) is a KIT-driven hematopoietic neoplasm characterized by the excessive accumulation of neoplastic mast cells (MCs) in various organs and, mainly, the bone marrow (BM). Multiple genetic and epigenetic mechanisms contribute to the onset and severity of SM. However, little is known to date about the metabolic underpinnings underlying SM aggressiveness, which has thus far impeded the development of strategies to leverage metabolic dependencies when existing KIT-targeted treatments fail. Read More

View Article and Full-Text PDF

Hereditary Alpha-Tryptasemia: a Commonly Inherited Modifier of Anaphylaxis.

Curr Allergy Asthma Rep 2021 May 10;21(5):33. Epub 2021 May 10.

Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 29B, Room 5NN18, MSC 1889, Bethesda, MD, 20892, USA.

Purpose Of Review: Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait and a common cause of elevated basal serum tryptase in Western populations. It is a risk factor for severe anaphylaxis among individuals with venom allergy and an established modifier of anaphylaxis and mast cell mediator-associated symptoms among patients with systemic mastocytosis. Understanding the physiology of tryptases and how this may relate to the clinical features associated with HαT is the first step in identifying optimal medical management and targets for novel therapeutics. Read More

View Article and Full-Text PDF

Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation.

Nat Commun 2021 05 5;12(1):2527. Epub 2021 May 5.

Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA.

Osteoporosis and other manifestations of bone disease are frequent in patients with systemic mastocytosis (SM) in association with the presence of mast cell infiltrates in bone marrow, although the mechanisms behind bone disease remain poorly understood. We find that extracellular vesicles (EVs) released by neoplastic mast cells and present in the serum of patients with SM (SM-EVs) block osteoblast differentiation and mineralization in culture, and when injected into mice diminish the expression of osteoblast markers, and trabecular bone volume and microarchitecture. We demonstrate that miRNA-30a and miRNA-23a, increased in SM-EVs and neoplastic mast cell-derived EVs, attenuate osteoblast maturation by suppressing expression of RUNX2 and SMAD1/5, essential drivers of osteogenesis. Read More

View Article and Full-Text PDF

Ripretinib and MEK Inhibitors Synergize to Induce Apoptosis in Preclinical Models of GIST and Systemic Mastocytosis.

Mol Cancer Ther 2021 May 4. Epub 2021 May 4.

Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts.

The majority of gastrointestinal stromal tumors (GIST) harbor constitutively activating mutations in KIT tyrosine kinase. Imatinib, sunitinib, and regorafenib are available as first-, second-, and third-line targeted therapies, respectively, for metastatic or unresectable KIT-driven GIST. Treatment of patients with GIST with KIT kinase inhibitors generally leads to a partial response or stable disease but most patients eventually progress by developing secondary resistance mutations in KIT. Read More

View Article and Full-Text PDF

Cutaneous Mastocytosis in Childhood-Update from the Literature.

J Clin Med 2021 Apr 2;10(7). Epub 2021 Apr 2.

"Carol Davila" University of Medicine and Pharmacy, 030167 Bucharest, Romania.

Mastocytosis (M) represents a systemic pathology characterized by increased accumulation and clonal proliferation of mast cells in the skin and/or different organs. Broadly, M is classified into two categories: Cutaneous mastocytosis (CM) and systemic mastocytosis (SM). In children, CM is the most frequent form. Read More

View Article and Full-Text PDF

Bone Marrow Mastocytosis: A Diagnostic Challenge.

J Clin Med 2021 Apr 1;10(7). Epub 2021 Apr 1.

Gruppo Interdisciplinare per lo Studio della Mastocitosi (GISM), Azienda Ospedaliera Universitaria Integrata di Verona, 37134 Verona, Italy.

Bone marrow mastocytosis (BMM) represents a provisional, indolent subvariant of systemic mastocytosis (SM). Utilizing WHO criteria, BMM requires bone marrow (BM) involvement and the absence of mastocytosis skin lesions. BMM is characterized by male sex prevalence, a slight increase of serum tryptase levels, low BM mast cells (MC) burden, and an indolent clinical course. Read More

View Article and Full-Text PDF

Prevalence of mastocytosis and hymenoptera venom allergy in the United States.

J Allergy Clin Immunol 2021 Apr 22. Epub 2021 Apr 22.

Division of Allergy and Clinical Immunology, Department of Internal Medicine, University of Michigan, Ann Arbor, Mich.

Background: Mastocytosis is a risk factor for hymenoptera venom anaphylaxis (HVA). Current guidelines recommend measuring tryptase in patients with HVA and that those with mastocytosis pursue lifelong venom immunotherapy (VIT). Available data on HVA and mastocytosis largely derive from European single-center studies, and the prevalence of HVA with and without mastocytosis in the United States is unknown. Read More

View Article and Full-Text PDF

Systemic Mastocytosis: Response to the Efficacy of Cladribine(2-CdA) with Current Terminology and Approach.

Indian J Hematol Blood Transfus 2021 Apr 31;37(2):329-330. Epub 2020 Aug 31.

Division of Hematology, Adnan Menderes University Medical Faculty, Aytepe Location, 09010 Efeler, Aydın Turkey.

View Article and Full-Text PDF

Metabolome and lipidome derangements during a severe mast cell activation event in a patient with indolent systemic mastocytosis.

J Allergy Clin Immunol 2021 Apr 20. Epub 2021 Apr 20.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.

Background: The number of mast cells in various organs is elevated manifold in individuals with systemic mastocytosis. Degranulation can lead to life-threatening symptomatology. No data about the alterations of the metabolome and lipidome during an attack have been published. Read More

View Article and Full-Text PDF

Molecular Background, Clinical Features and Management of Pediatric Mastocytosis: Status 2021.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, 1090 Vienna, Austria.

Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline mutations in the proto-oncogene are detected in most patients. Cutaneous mastocytosis is the most common form of the disease in children. Read More

View Article and Full-Text PDF

Adverse Prognostic Impact of the D816V Transcriptional Activity in Advanced Systemic Mastocytosis.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, 68167 Mannheim, Germany.

In systemic mastocytosis (SM), qualitative and serial quantitative assessment of the D816V mutation is of diagnostic and prognostic relevance. We investigated peripheral blood and bone marrow samples of 161 patients (indolent SM (ISM), = 40; advanced SM, AdvSM, = 121) at referral and during follow-up for the D816V variant allele frequency (VAF) at the DNA-level and the D816V expressed allele burden (EAB) at the RNA-level. A round robin test with four participating laboratories revealed an excellent correlation ( > 0. Read More

View Article and Full-Text PDF

Response Criteria in Advanced Systemic Mastocytosis: Evolution in the Era of KIT Inhibitors.

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

Division of Hematology, School of Medicine, Stanford Cancer Institute/Stanford University, 875 Blake Wilbur Drive, Stanford, CA 94305-6555, USA.

Systemic mastocytosis (SM) is a rare clonal hematologic neoplasm, driven, in almost all cases, by the activating D816V mutation that leads to the growth and accumulation of neoplastic mast cells. While patients with advanced forms of SM have a poor prognosis, the introduction of KIT inhibitors (e.g. Read More

View Article and Full-Text PDF

Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis.

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

Department of Allergology, Medical University of Gdansk, 80-211 Gdansk, Poland.

Systemic mastocytosis (SM) is a hematologic neoplasm with abnormal accumulation of mast cells in various organ systems such as the bone marrow, other visceral organs and skin. So far, only little is known about epigenetic changes contributing to the pathogenesis of SM. In the current article, we provide an overview of epigenetic changes that may occur and be relevant to mastocytosis, including mutations in genes involved in epigenetic processes, such as , and , and global and gene-specific methylation patterns in neoplastic cells. Read More

View Article and Full-Text PDF

Mediator-Related Symptoms and Anaphylaxis in Children with Mastocytosis.

Int J Mol Sci 2021 Mar 7;22(5). Epub 2021 Mar 7.

Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria.

Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Read More

View Article and Full-Text PDF

Real-World Efficacy of Midostaurin in Aggressive Systemic Mastocytosis.

J Clin Med 2021 Mar 7;10(5). Epub 2021 Mar 7.

Chair and Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin Staszica Street 11, 20-081 Lublin, Poland.

In April 2017 midostaurin was approved by the US Food and Drug Administration for the treatment of patients with aggressive systemic mastocytosis (ASM). So far, very limited real world data on its efficacy is available. Thirteen patients aged from 48 to 79 years, who received midostaurin in the early access program, were included in the study. Read More

View Article and Full-Text PDF

Severe cold urticaria can point to an underlying clonal mast cell disorder.

Allergy 2021 Apr 2. Epub 2021 Apr 2.

Department of Dermatology and Allergy, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Dermatological Allergology, Allergie-Centrum Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany.

View Article and Full-Text PDF

Impaired endothelial function irrespective of systemic inflammation or atherosclerosis in mastocytosis.

Ann Allergy Asthma Immunol 2021 Mar 26. Epub 2021 Mar 26.

Division of Immunology and Allergic Diseases, Department of Internal Medicine, İstanbul Faculty of Medicine, İstanbul University, İstanbul, Turkey. Electronic address:

Background: Knowledge on endothelial dysfunction and its relation to atherosclerosis in mastocytosis is limited.

Objective: To investigate the endothelial function in mastocytosis by flow-mediated dilatation (FMD) and biomarkers related to vascular endothelia and to evaluate its relationship with the presence of subclinical atherosclerosis by carotid intima media thickness (CIMT).

Methods: A total of 49 patients with mastocytosis and 25 healthy controls (HCs) were included. Read More

View Article and Full-Text PDF

Proceedings from the Inaugural American Initiative in Mast Cell Diseases (AIM) Investigator Conference.

J Allergy Clin Immunol 2021 Jun 11;147(6):2043-2052. Epub 2021 Mar 11.

Division of Allergy and Immunology, University of Michigan, Ann Arbor, Mich.

The American Initiative in Mast Cell Diseases (AIM) held its inaugural investigator conference at Stanford University School of Medicine in May 2019. The overarching goal of this meeting was to establish a Pan-American organization of physicians and scientists with multidisciplinary expertise in mast cell disease. To serve this unmet need, AIM envisions a network where basic, translational, and clinical researchers could establish collaborations with both academia and biopharma to support the development of new diagnostic methods, enhanced understanding of the biology of mast cells in human health and disease, and the testing of novel therapies. Read More

View Article and Full-Text PDF

The Genetic Basis and Clinical Impact of Hereditary Alpha-Tryptasemia.

J Allergy Clin Immunol Pract 2021 Jun 17;9(6):2235-2242. Epub 2021 Mar 17.

Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address:

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait found in 4% to 6% of the general population and defined by excess copies of alpha-tryptase at TPSAB1. Elevated basal serum tryptase (sBT >8 ng/mL) is a defining feature of HαT and appears to result from increased pro-alpha-tryptase synthesis and secretion rather than mast cell activation. It is estimated that approximately one-third of individuals with HαT have associated symptoms, including cutaneous, gastrointestinal, atopic, musculoskeletal, autonomic, and neuropsychiatric manifestations. Read More

View Article and Full-Text PDF

Omalizumab ensures compatibility to bee venom immunotherapy (VIT) after VIT-induced anaphylaxis in a patient with systemic mastocytosis.

Allergol Select 2021 11;5:128-132. Epub 2021 Mar 11.

Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Luebeck.

Background: Systemic reactions and anaphylaxis due to Hymenoptera venoms occur in up to 7.5% of the European population. Fatal sting reactions are very rare. Read More

View Article and Full-Text PDF

Systemic mastocytosis with flushing and hypotension: A case report and literature review.

Exp Ther Med 2021 Apr 25;21(4):404. Epub 2021 Feb 25.

Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

Systemic mastocytosis (SM) is a heterogeneous disease of the bone marrow, which is characterized by the abnormal proliferation and infiltration of mast cells in one or more organs, such as the skin, bone marrow, digestive tract, liver and spleen. Urticaria pigmentosa is a typical but infrequent manifestation of SM. Other clinical presentations are non-specific, varying from pruritus and hypotension to multiple organ dysfunction, which may be lethal when hemodynamic changes occur, such as the sharp decline in blood pressure observed in the present case. Read More

View Article and Full-Text PDF

Vascular endothelial growth factors and angiopoietins as new players in mastocytosis.

Clin Exp Med 2021 Mar 9. Epub 2021 Mar 9.

Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy.

Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects. Read More

View Article and Full-Text PDF