Evaluation of the prognostic relevance of <scp>l</scp>‐selectin and ICAM1 expression in myelodysplastic syndromes

Buccisano, Francesco; Maurillo, Luca; Tamburini, Anna; Poeta, Giovanni Del; Principe, Maria Ilaria Del; Ammatuna, Emanuele; Consalvo, Maria Irno; Campagna, Selenia; Ottaviani, Licia; Sarlo, Chiara; Renzi, Daniela; Faccia, Sabrina; Fraboni, Daniela; Coco, Francesco Lo; Amadori, Sergio; Venditti, Adriano

doi:10.1111/j.1600-0609.2007.00986.x

Cited by 8 publications

(5 citation statements)

References 45 publications

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“…L-selectin is expressed on CD34 ϩ stem cells, 42 and although it is not clear what the exact role for L-selectin is during bone marrow development, 41 impaired L-selectin signaling in CD34 ϩ cells is implicated in myelodysplastic syndromes. 43 Our data raise the possibility that WASp I294T may in part perturb hematopoiesis through disruption of normal cell-cell and cell-matrix contacts in bone marrow niches; this warrants further investigation.…”

Section: Wasp I294t Affects Lymphocyte Adhesion Under Flow 5363mentioning

confidence: 76%

A congenital activating mutant of WASp causes altered plasma membrane topography and adhesion under flow in lymphocytes

Burns

Killock

Moulding

et al. 2010

Blood

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Leukocytes rely on dynamic actindependent changes in cell shape to pass through blood vessels, which is fundamental to immune surveillance. WiskottAldrich Syndrome protein (WASp) is a hematopoietic cell-restricted cytoskeletal regulator important for modulating cell shape through Arp2/3-mediated actin polymerization. A recently identified WASp I294T mutation was shown to render WASp constitutively active in vivo, causing increased filamentous (F)-actin polymerization, high podosome turnover in macrophages, and myelodysplasia. The aim of this study was to determine the effect of WASp I294T expression in lymphocytes. Here, we report that lymphocytes isolated from a patient with WASp I294T , and in a cellular model of WASp I294T IntroductionThe Wiskott-Aldrich Syndrome protein (WASp) is a key cytoskeletal regulator in hematopoietic cells. 1 Through its multidomain structure, WASp integrates inputs from disparate signaling pathways to initiate and regulate Arp2/3-mediated actin polymerization. This is important for the normal formation of various actin-rich structures including the T-cell immune synapse, phagocytic cups, and specialized adhesion structures called podosomes in myeloid cells. [2][3][4] The majority of human disease-causing mutations in WASp are hypomorphic or null loss of function mutations, which result in Wiskott-Aldrich Syndrome (WAS). 5 Patients with WAS classically suffer from thrombocytopenia, eczema, and a broad immunodeficiency, reflecting the functional deficiency of almost all hematopoietic lineages.Recently, 3 novel human mutations (L270P, S272P, and I294T) leading to constitutive WASp activation have been reported to cause a distinct disease, X-linked neutropoenia (XLN). 6,7 All 3 are positioned in the GTPase binding domain (GBD; residues 230-288) of WASp and disrupt its autoinhibitory interaction with the Arp2/3 binding, C-terminal verprolin homology, central, acidic (VCA) domain. The result is enhanced and dysregulated WASp activity characterized by an increase in cellular filamentous (F)-actin and abnormalities of actin cytoskeletal structure and dynamics. A large kindred bearing the rare I294T mutation was recently reported, informing our understanding of the clinical spectrum of WASp I294T disease, which appears variable but is usually associated with neutropoenia and recurrent infections. 7,8 Although fatal infections have been described, infectious complications are surprisingly mild and not correlated with the degree of neutropoenia. 8 Other immunopathology is also seen, including low levels of CD4 and CD8 T cells, natural killer (NK) cell and B-cell lymphopenia, and reduced levels of IgA. To date, specific cellular effects have only been examined in myeloid cells, where defects of myelopoiesis and podosome formation have been reported. 7,9 Our aim in this report was to determine whether WASp I294T also attenuates aspects of lymphocyte function.The lymphocyte surface is dominated by microvilli: prominent actin-rich, fingerlike membrane projections involved in mediating cell-c...

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Section: Wasp I294t Affects Lymphocyte Adhesion Under Flow 5363mentioning

confidence: 76%

A congenital activating mutant of WASp causes altered plasma membrane topography and adhesion under flow in lymphocytes

Burns

Killock

Moulding

et al. 2010

Blood

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“…Some studies have proved that CD54 is abnormally highly expressed in a variety of malignant tumors, which promotes the occurrence and development of tumors and affects their prognosis. Several studies have shown that CD54 is highly expressed in CD34+ cells and CD8+ lymphocytes in MDS patients, and the soluble CD54 level in plasma of MDS is also significantly increased, which is an important indicator of cytopenia, dysplasia, and disease progression to AML ( 10 – 14 ).…”

Section: Discussionmentioning

confidence: 99%

Increased Circulating of CD54highCD181low Neutrophils in Myelodysplastic Syndrome

Yang

Liu

et al. 2021

Front. Oncol.

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Myelodysplastic syndromes (MDSs) are a group of heterogeneous hematopoietic stem/progenitor cells clonal diseases, characteristic features with myeloid dysplasia, leading to abnormality of neutrophils. Recent studied have showed that neutrophils act not only as professional killers, but also as regulators of innate and adaptive immune in infection and inflammatory condition. The CD54highCD181low neutrophils are a kind of reverse-transmigrated neutrophils characterized proinflammatory phenotype. We investigated the frequency and functional properties of circulating CD54highCD181low neutrophils in patients with untreated MDS. Frequency of CD54highCD181low neutrophils was significantly increased in MDS patients and related to the severity of the disease. Furthermore, CD54highCD181low neutrophils suppressed CD8+ T cells functions in vitro. CD54highCD181low neutrophils lead to upregulation of PD1 on CD8+ T cells. Higher CD54highCD181low neutrophils were related to poor prognosis and more infections. The frequency of CD54highCD181low neutrophils decreased in high risk MDS patients who had response after treatment with decitabine. Overall, we identified CD54highCD181low neutrophils expanded in MDS. The exact mechanisms of increased CD54highCD181low neutrophils and its effect on immune function remain to be elucidated.

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“…We also validated the expression of these 5 genes using a new dataset and analyzed their diagnostic value for AML using a random ferns classifier. Typically, shed forms of SELL are often studied in conjunction with AML, and plasma from AML patients shows high levels of shed forms of selections [14][15][16]. Little attention has been paid to the amount of SELL expressed in AML bone marrow.…”

Section: Fig 8 the Relationship Between Different Gene Expressions An...mentioning

confidence: 99%

Exploring the relationship between immune heterogeneity characteristic genes of rheumatoid arthritis and acute myeloid leukemia

Jiang,

Liu

et al. 2024

Discov Onc

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Background People with autoimmune diseases are prone to cancer, and there is a close relationship between rheumatoid arthritis (RA) and acute myeloid leukemia (AML). The bone marrow (BM) is affected throughout the course of RA, with a variety of hematologic involvement. Hopes are pinned on rheumatoid arthritis research to obtain BM biomarkers for AML. Methods Synovial transcriptome sequencing data for RA and osteoarthritis (OA), and single-cell sequencing data for RA and controls were obtained from the GEO database.Bone marrow sequencing data for AML patients and normal subjects were obtained from the UCSC Xena database. The final immune heterogeneity characteristics of RA were determined through ssGSEA analysis, gene differential expression analysis, fuzzy c-means clustering algorithm, and XGboost algorithm. Random Ferns classifiers (RFs) are used to identify new bone marrow markers for AML. Results SELL, PTPRC, IL7R, CCR7, and KLRB1 were able to distinguish leukemia cells from normal cells well, with AUC values higher than 0.970. Conclusion Genes characterizing the immune heterogeneity of RA are associated with AML, and KLRBA may be a potential target for AML treatment.

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Evaluation of the prognostic relevance of l‐selectin and ICAM1 expression in myelodysplastic syndromes

Abstract: (i) L-selectin is defective in the stem cell compartment of MDS and sAML, whereas ICAM1 is overexpressed; (ii) the ratio of their expression has a prognostic role; and (iii) a ratio <1 significantly predicts progression to overt leukaemia in MDS patients.

Cited by 8 publications

References 45 publications

A congenital activating mutant of WASp causes altered plasma membrane topography and adhesion under flow in lymphocytes

A congenital activating mutant of WASp causes altered plasma membrane topography and adhesion under flow in lymphocytes

Increased Circulating of CD54highCD181low Neutrophils in Myelodysplastic Syndrome

Exploring the relationship between immune heterogeneity characteristic genes of rheumatoid arthritis and acute myeloid leukemia

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