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The American Journal of the Medical... Mar 2017Mast cell activation syndrome (MCAS), a recently recognized nonneoplastic mast cell disease driving chronic multisystem inflammation and allergy, appears prevalent and...
BACKGROUND
Mast cell activation syndrome (MCAS), a recently recognized nonneoplastic mast cell disease driving chronic multisystem inflammation and allergy, appears prevalent and thus important. We report the first systematic characterization of a large MCAS population.
METHOD
Demographics, comorbidities, symptoms, family histories, physical examination and laboratory findings were reviewed in 298 retrospective and 115 prospective patients with MCAS. Blood samples from prospective subjects were examined by flow cytometry for clonal mast cell disease and tested for cytokines potentially driving the monocytosis frequent in MCAS.
RESULTS
Demographically, white females dominated. Median ages at symptom onset and diagnosis were 9 and 49 years, respectively (range: 0-88 and 16-92, respectively) and median time from symptom onset to diagnosis was 30 years (range: 1-85). Median numbers of comorbidities, symptoms, and family medical issues were 11, 20, and 4, respectively (range: 1-66, 2-84, and 0-33, respectively). Gastroesophageal reflux, fatigue and dermatographism were the most common comorbidity, symptom and examination finding. Abnormalities in routine laboratories were common and diverse but typically modest. The most useful diagnostic markers were heparin, prostaglandin D, histamine and chromogranin A. Flow cytometric and cytokine assessments were unhelpful.
CONCLUSIONS
Our study highlights MCAS׳s morbidity burden and challenging heterogeneity. Recognition is important given good survival and treatment prospects.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Child; Child, Preschool; Chromogranin A; Female; Heparin; Histamine; Humans; Infant; Infant, Newborn; Male; Mastocytosis; Middle Aged; Prospective Studies; Prostaglandin D2; Retrospective Studies; Syndrome; Young Adult
PubMed: 28262205
DOI: 10.1016/j.amjms.2016.12.013 -
British Journal of Haematology May 2014Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic stem cell disorder with myelodysplastic and myeloproliferative overlap features, and an inherent... (Review)
Review
Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic stem cell disorder with myelodysplastic and myeloproliferative overlap features, and an inherent tendency to transform to acute myeloid leukaemia. Approximately 30% of patients present with clonal cytogenetic abnormalities, while almost 90% have molecular aberrations involving epigenetic regulation, the spliceosome component machinery, tumour suppressor genes and transcription factors/regulators. Numerous prognostic models exist for CMML, with more recent models incorporating prognostic mutations, such as those involving ASXL1. Other variables that seem to consistently affect outcomes include the degree of leucocytosis/monocytosis, anaemia and thrombocytopenia. Allogeneic stem cell transplant remains the only curative option for CMML, while hypomethylating agents can be used for transplant-ineligible patients or those without suitable stem cell sources. Targeting biological pathways activated in CMML offers potential hope for more effective and less toxic therapies.
Topics: Humans; Leukemia, Myelomonocytic, Chronic; Prognosis; Stem Cell Transplantation; Transplantation, Homologous
PubMed: 24467717
DOI: 10.1111/bjh.12756 -
Seminars in Hematology Jul 2022Large scale high-throughput DNA sequencing studies have identified clonal hematopoiesis (CH) as a clinical phenomenon characterized by a disproportionately large clonal... (Review)
Review
Large scale high-throughput DNA sequencing studies have identified clonal hematopoiesis (CH) as a clinical phenomenon characterized by a disproportionately large clonal population in the hematopoietic system with a shared mutational background. CH originates through mutations in hematopoietic stem and progenitor cells (HSPCs) which provide a proliferative advantage over unmutated HSPCs and has been characterized as a risk factor for myeloid neoplasm (MN) development. Large population studies found that CH is an age-related event which is commonly found in association with milder phenotypes such as cytopenia, mild monocytosis, intravascular hemolysis, or chronic inflammation. More importantly, the vast majority of individuals with CH are asymptomatic and healthy people of advanced age, where the impact of CH is thus considered to be of indeterminate potential (CHIP). These conditions are sometimes referred to as benign to facilitate distinction from overt MN but, despite this definition, may still result in severe illness, reduced overall survival, and increased risk of hematologic neoplasms development and all-cause mortality. The purpose of this review is to describe clinical conditions associated with CH, the clinical significance of CH-related clinical phenotypes, and the determinants of progression from CH to overt MN following the paradigmatic example of SF3B1-driven CH.
Topics: Clonal Hematopoiesis; Hematologic Neoplasms; Hematopoiesis; Hematopoietic Stem Cells; Humans; Myeloproliferative Disorders; Phosphoproteins; RNA Splicing Factors
PubMed: 36115692
DOI: 10.1053/j.seminhematol.2022.08.002 -
Blood Nov 2016Exome sequencing studies in chronic myelomonocytic leukemia (CMML) illustrate a mutational landscape characterized by few somatic mutations involving a subset of... (Review)
Review
Exome sequencing studies in chronic myelomonocytic leukemia (CMML) illustrate a mutational landscape characterized by few somatic mutations involving a subset of recurrent gene mutations in ASXL1, SRSF2, and TET2, each approaching 40% in incidence. This has led to the clinical implementation of next-generation sequencing panels that effectively identify clonal monocytosis and complement clinical prognostic scoring systems in most patients. However, most murine models based on single gene mutations fail to recapitulate the CMML phenotype, and many gene mutations are loss of function, making the identification of traditional therapeutic vulnerabilities challenging. Further, as a subtype of the myelodysplastic/myeloproliferative neoplasms, CMML has a complex clinical heterogeneity not reflected by the mutational landscape. In this review, we will discuss the discordance between mutational homogeneity and clinical complexity and highlight novel genomic and nongenomic approaches that offer insight into the underlying clinical characteristics of CMML.
Topics: Disease Progression; Genetic Heterogeneity; Genomics; High-Throughput Nucleotide Sequencing; Humans; Leukemia, Myelomonocytic, Chronic; Mutation; Phenotype; Prognosis
PubMed: 27707735
DOI: 10.1182/blood-2016-07-692988 -
Frontiers in Oncology 2021Atypical chronic myelogenous leukemia (aCML), negative is a rare myelodysplastic/myeloproliferative neoplasm, usually manifested with hyperleukocytosis without... (Review)
Review
Atypical chronic myelogenous leukemia (aCML), negative is a rare myelodysplastic/myeloproliferative neoplasm, usually manifested with hyperleukocytosis without monocytosis or basophilia, organomegaly, and marked dysgranulopoiesis. In this review, we will discuss the classification and diagnostic criteria of aCML, as these have been formulated during the past 30 years, with a focus on the recent advances in the molecular characterization of the disease. Although this entity does not have a definitive molecular profile, its molecular characterization has contributed to a better understanding and more accurate classification and diagnosis of aCML. At the same time, it has facilitated the identification of adverse prognostic factors and the stratification of patients according to their risk for leukemic transformation. What is more, the molecular characterization of the disease has expanded our therapeutic choices, thoroughly presented and analyzed in this review article.
PubMed: 34868917
DOI: 10.3389/fonc.2021.722507 -
Critical Reviews in Oncology/hematology Aug 2015Chronic myelomonocytic leukemia (CMML) includes components of both myelodysplastic syndrome and myeloproliferative neoplasms and is associated with a characteristic... (Review)
Review
Chronic myelomonocytic leukemia (CMML) includes components of both myelodysplastic syndrome and myeloproliferative neoplasms and is associated with a characteristic peripheral monocytosis. CMML is caused by the proliferation of an abnormal hematopoietic stem cell clone and may be influenced by microenvironmental changes. The disease is rare and has undergone revisions in its classification. We review the recent classification strategies as well as diagnostic criteria, focusing on CMML's genetic alterations and unique pathophysiology. We also discuss the latest molecular characterization of the disease, including how molecular factors affect current prognostic models. Finally, we focus on available treatment strategies, with a special emphasis on experimental and forthcoming therapies.
Topics: Hematopoietic Stem Cells; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Stem Cell Niche; Tumor Microenvironment
PubMed: 25869097
DOI: 10.1016/j.critrevonc.2015.03.002 -
Annales de Biologie Clinique Oct 2019The discovery of a monocytosis is a frequent phenomenon, requiring confirmation by reading under a microscope by an experimented biologist, to overcome usual cytological... (Review)
Review
The discovery of a monocytosis is a frequent phenomenon, requiring confirmation by reading under a microscope by an experimented biologist, to overcome usual cytological traps such as the presence of hairy cells, promonocytes or monoblasts. In the vast majority of cases the secondary origin is very easily found by the context and/or the presence of a biological inflammatory syndrome. More rarely the diagnosis is directed towards an eosinophilic pathology or an acute leukemia. In other cases, CMML, MPN or MDS with monocytosis may be highlighted. In the absence of any pathognomonic element and the presence of "borderline" forms the differential diagnosis between these 3 entities is not always straightforward, requiring, according to WHO, molecular investigations and elimination of any reactive cause of monocytosis. Although histological, immunohistochemical and phenotypic flow cytometric studies are not currently recommended by WHO, these investigations could be of interest in the evaluation of difficult cases.
Topics: Adult; Age of Onset; Algorithms; Clinical Laboratory Techniques; Diagnosis, Differential; Humans; Leukocyte Count; Monocytes; Myelodysplastic Syndromes
PubMed: 31486402
DOI: 10.1684/abc.2019.1475 -
Scientific Reports Oct 2020Bone marrow erythropoiesis is mainly homeostatic and a demand of oxygen in tissues activates stress erythropoiesis in the spleen. Here, we show an increase in the number...
Bone marrow erythropoiesis is mainly homeostatic and a demand of oxygen in tissues activates stress erythropoiesis in the spleen. Here, we show an increase in the number of circulating erythrocytes in apolipoprotein E mice fed a Western high-fat diet, with similar number of circulating leukocytes and CD41 events (platelets). Atherogenic conditions increase spleen erythropoiesis with no variations of this cell lineage in the bone marrow. Spleens from atherogenic mice show augmented number of late-stage erythroblasts and biased differentiation of progenitor cells towards the erythroid cell lineage, with an increase of CD71CD41CD34CD117Sca1Lin cells (erythroid-primed megakaryocyte-erythroid progenitors), which is consistent with the way in which atherogenesis modifies the expression of pro-erythroid and pro-megakaryocytic genes in megakaryocyte-erythroid progenitors. These data explain the transiently improved response to an acute severe hemolytic anemia insult found in atherogenic mice in comparison to control mice, as well as the higher burst-forming unit-erythroid and colony forming unit-erythroid capacity of splenocytes from atherogenic mice. In conclusion, our work demonstrates that, along with the well stablished enhancement of monocytosis during atherogenesis, stress erythropoiesis in apolipoprotein E mice fed a Western high fat diet results in increased numbers of circulating red blood cells.
Topics: Animals; Antigens, CD; Atherosclerosis; Cell Differentiation; Erythroid Precursor Cells; Erythropoiesis; Hematopoiesis, Extramedullary; Mice; Mice, Knockout, ApoE; Spleen; Stress, Physiological
PubMed: 33116141
DOI: 10.1038/s41598-020-74665-x -
Journal of Cancer 2018To measure hematologic parameters derived from the white blood cell (WBC) count and differential count (DC) as prognostic factors for survival in patients with stage IB...
To measure hematologic parameters derived from the white blood cell (WBC) count and differential count (DC) as prognostic factors for survival in patients with stage IB and IIA cervical cancer. We retrospectively examined demographic, clinicopathologic, and laboratory parameters in a cohort of 233 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer who underwent surgical resection. We further assessed the effects of the WBC count and DC-derived hematologic parameters on progression-free survival (PFS) and overall survival (OS) after controlling for other parameters. Patients were followed up for a median of 46.6 months (range, 9-142 months). The Kaplan-Meier estimates of PFS and OS at 5 years were 88.5% and 92.3%, respectively. In a multivariate analysis, we identified the absolute monocyte count (AMC) (hazard ratio [HR], 11.78; <0.001) and tumor size (HR, 5.41; = 0.003) as the strongest prognostic factors affecting PFS. We also identified AMC (HR, 23.29; <0.001), tumor size, (HR, 5.27; = 0.033), and lymph node involvement (HR, 3.90; = 0.027) as the strongest prognostic factors affecting OS. AMC remained prognostic with respect to PFS or OS in a Cox model that controlled for the neutrophil-lymphocyte ratio or lymphocyte-monocyte ratio, although neither ratio was a significant prognostic factor for survival. Monocytosis and an increased tumor size were found to be independent prognostic factors affecting both PFS and OS in patients with stage IB and IIA cervical cancer.
PubMed: 29290770
DOI: 10.7150/jca.22234 -
European Journal of Pediatrics Sep 2021We report the clinical characteristics and management of fourteen neonates and very young infants with COVID-19. Although all presented with mild symptoms and did not...
We report the clinical characteristics and management of fourteen neonates and very young infants with COVID-19. Although all presented with mild symptoms and did not require specific treatment, most of them had abnormal laboratory and radiological findings. Ten infants presented with neutropenia and/or monocytosis but none with lymphopenia. Transient hypertriglyceridemia and/or prolonged viral shedding were detected in 9 patients.Conclusion: Based to our experience, COVID-19 is mild in very young infants and might have distinct laboratory findings. What is Known: • SARS-CoV-2 in infants is a mild disease. • The period of transmission is approximately 2 weeks. What is New: • Very young age is not a risk factor for severe COVID-19 but could be associated with prolonged viral shedding. • Neutropenia and monocytosis are distinct characteristics of COVID-19 in very young infants.
Topics: COVID-19; Humans; Infant; Infant, Newborn; Risk Factors; SARS-CoV-2
PubMed: 33786658
DOI: 10.1007/s00431-021-04042-x