Mixed‐lineage eosinophil/basophil crisis in MDS: a rare form of progression

Wimazal, Friedrich; Baumgartner, Christian; Sonneck, Karoline; Zauner, Christian; Geissler, Philipp; Schur, Sophie; Samorapoompichit, Puchit; Müllauer, Leonhard; Födinger, Manuela; Agis, Hermine; Sperr, Wolfgang R.; Valent, Peter

doi:10.1111/j.1365-2362.2008.01950.x

Cited by 15 publications

(17 citation statements)

References 57 publications

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“…Similar phenotypes were also observed in the bone marrow compartment of an U2AF1 S34F -transgenic mouse model (26): U2AF1 S34F mice showed a significant decrease in monocytes, together with a significant increase in granulocyte neutrophils in the bone marrow, compared with control mice (26). Interestingly, eosinophilia has been reported in some patients with de novo MDS (35, 36). Our study demonstrates a link between U2AF1 S34F and skewed granulomonocytic differentiation in human hematopoiesis.…”

Section: Discussionmentioning

confidence: 99%

The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes

Yip¹,

Steeples²,

Repapi³

et al. 2017

Journal of Clinical Investigation

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Mutations of the splicing factor–encoding gene U2AF1 are frequent in the myelodysplastic syndromes (MDS), a myeloid malignancy, and other cancers. Patients with MDS suffer from peripheral blood cytopenias, including anemia, and an increasing percentage of bone marrow myeloblasts. We studied the impact of the common U2AF1S34F mutation on cellular function and mRNA splicing in the main cell lineages affected in MDS. We demonstrated that U2AF1S34F expression in human hematopoietic progenitors impairs erythroid differentiation and skews granulomonocytic differentiation toward granulocytes. RNA sequencing of erythroid and granulomonocytic colonies revealed that U2AF1S34F induced a higher number of cassette exon splicing events in granulomonocytic cells than in erythroid cells. U2AF1S34F altered mRNA splicing of many transcripts that were expressed in both cell types in a lineage-specific manner. In hematopoietic progenitors, the introduction of isoform changes identified in the U2AF1S34F target genes H2AFY, encoding an H2A histone variant, and STRAP, encoding serine/threonine kinase receptor–associated protein, recapitulated phenotypes associated with U2AF1S34F expression in erythroid and granulomonocytic cells, suggesting a causal link. Furthermore, we showed that isoform modulation of H2AFY and STRAP rescues the erythroid differentiation defect in U2AF1S34F MDS cells, suggesting that splicing modulators could be used therapeutically. These data have critical implications for understanding MDS phenotypic heterogeneity and support the development of therapies targeting splicing abnormalities.

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Section: Discussionmentioning

confidence: 99%

The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes

Yip¹,

Steeples²,

Repapi³

et al. 2017

Journal of Clinical Investigation

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“…IgG is the predominant antibody in secondary immune responses. IgG subclasses (e.g., IgG1, IgG2, IgG3, IgG4) activate blood complement cascades through complex pathways to promote cell lysis or to activate other inflammatory cells such as MUs [1,40,107,[118][119][120][121][122][123][124][125][126][127][128][129]. Baso and Eos are also activated during inflammatory conditions and/or helminthic infections, often providing response profiles that are characteristics or complementary to MCs responses [1,22,40,57,111,118,[125][126][127].…”

Section: Shared and Specialized Features Of Innate And Adaptive Immunmentioning

confidence: 97%

“…Parasitic infections and allergen-induced inflammatory responses involving MCs sensitization are often initiated by activation of B lymphocytes (B cells) that act as APCs for recognition and processing of antigenic components. Activation of B cells involves proliferation to plasma cells and production of antigen-specific antibodies (e.g., IgE, IgA, IgM, or IgG isotypes) followed by activation and sensitization of MCs; activation of blood complement cascades to aid MCs in cell lysis, activation of goblet cells (GCs) for mucus production as well as generation of antigen-specific memory cells [1,15,33,40,50,58,59,108,[116][117][118][119][120][121][122][123][124][125][126]. IgG is the predominant antibody in secondary immune responses.…”

Section: Shared and Specialized Features Of Innate And Adaptive Immunmentioning

confidence: 99%

“…Within the innate immune system, MCs are known as unique effector cells due to their high affinity Fc-epsilon receptor (FceR) that bind to antigen-specific IgE antibodies in response to parasitic infections, allergens (e.g., pollenragweed, dust mite) or protein complexes (e.g., fluoresceinconjugated ovalbumin/FLOA), and a variety of drugs and foods that induce allergies and/or tumor growth [1,15,33,40,48,50,58,59,70,72,85,[114][115][116][117][118][119][120][121][122][123]. Parasitic infections and allergen-induced inflammatory responses involving MCs sensitization are often initiated by activation of B lymphocytes (B cells) that act as APCs for recognition and processing of antigenic components.…”

Section: Shared and Specialized Features Of Innate And Adaptive Immunmentioning

confidence: 99%

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Inflammation, Aging, and Cancer: Tumoricidal Versus Tumorigenesis of Immunity

Khatami

2009

Cell Biochem Biophys

100

168

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Acute inflammation is a highly regulated defense mechanism of immune system possessing two well-balanced and biologically opposing arms termed apoptosis ('Yin') and wound healing ('Yang') processes. Unresolved or chronic inflammation (oxidative stress) is perhaps the loss of balance between 'Yin' and 'Yang' that would induce co-expression of exaggerated or 'mismatched' apoptotic and wound healing factors in the microenvironment of tissues ('immune meltdown'). Unresolved inflammation could initiate the genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. In this perspective 'birds' eye' view of major interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting ('tumoricidal') or growth-promoting ('tumorigenic') properties of immune cells and the genesis of chronic inflammatory diseases and cancer will be discussed. Persistent inflammation is perhaps a common denominator in the genesis of nearly all age-associated health problems or cancer. Future challenging opportunities for diagnosis, prevention, and/or therapy of chronic illnesses will require an integrated understanding and identification of developmental phases of inflammation-induced immune dysfunction and age-associated hormonal and physiological readjustments of organ systems. Designing suitable cohort studies to establish the oxido-redox status of adults may prove to be an effective strategy in assessing individual's health toward developing personal medicine for healthy aging.

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“…However, even in patients with markedly increased numbers of eosinophils, the clinical course can be stable for years without any signs of rapid disease progression, such as an increase in blasts [9]. In a case report by Bakotic et al [10], a 76-year-old male patient with MDS showing cytologically atypical BM and peripheral blood eosinophilia in association with ring chromosome 7, had favorable survival without disease progression with supportive care even though the patient presented with chromosomal abnormality.…”

Section: Discussionmentioning

confidence: 99%

A case of myelodysplastic syndrome with marked eosinophilia showing favorable prognosis

et al. 2013

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Myelodysplastic syndrome (MDS) with eosinophilia is a rare condition and has yet to be classified under the 2008 World Health Organization classification. However, reports have described the prognostic significance of chronic persistent eosinophilia in MDS. Here, we report a case of a 67-year-old woman who was admitted to the hospital in July 2007 with generalized weakness, dizziness, and dyspnea on exertion persisting for 5 years. In the initial investigation, eosinophilia (22.1%) in peripheral blood and an increased proportion of eosinophils (5.6%) in normocellular bone marrow with dysplastic megakaryocytes and erythroid cells were noted. Eosinophilia was continuously detected during follow-up over 3 years. In a second bone marrow examination in August 2010, hypercellular bone marrow with similar features was observed. These findings led to the diagnosis of MDS with chronic persistent eosinophilia. To increase awareness of the prognostic significance of MDS with chronic eosinophilia, here we report a slow-progressing case of MDS with chronic persistent eosinophilia lasting over 6 years.

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Mixed‐lineage eosinophil/basophil crisis in MDS: a rare form of progression

Abstract: Mixed basophil/eosinophil crisis may develop in patients with MDS but is an extremely rare event.

Cited by 15 publications

References 57 publications

The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes

The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes

Inflammation, Aging, and Cancer: Tumoricidal Versus Tumorigenesis of Immunity

A case of myelodysplastic syndrome with marked eosinophilia showing favorable prognosis

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