Both granulocytic and non-granulocytic blood cells are affected in patients with severe congenital neutropenia and their non-neutropenic family members: An evaluation of morphology, function, and cell death [Ciddi konjenital nötropenisi olan hastalarda ve nötropenik olmayan ebeveynlerinde hem granülositik hem granülositik olmayan kan hücreleri etkilenir: Morfoloji, fonksiyon ve hücre ölümü yönünden bir değerlendirme]

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dc.contributor.authorOlcay L.
dc.contributor.authorÜnal Ş.
dc.contributor.authorOnay H.
dc.contributor.authorErdemli E.
dc.contributor.authorÖztürk A.
dc.contributor.authorBillur D.
dc.contributor.authorİkincioğulları A.
dc.date.accessioned2021-05-03T20:48:11Z
dc.date.available2021-05-03T20:48:11Z
dc.date.issued2018
dc.description.abstractObjective: To examine granulocytic and non-granulocytic cells in children with severe congenital neutropenia (SCN) and their non-neutropenic parents. Materials and Methods: Fifteen patients with SCN and 21 non-neutropenic parents were evaluated for a) CD95, CD95 ligand, annexin V, propidium iodide, cell cycle, and lymphocyte subsets by flow cytometry; b) rapid cell senescence (of leukocytes) by senescence-associated ?-galactosidase stain; c) aggregation tests by aggregometer; d) in vitro bleeding time by PFA-100 instrument; e) mepacrine-labeled dense granule number of thrombocytes by fluorescence microscope; and f) hematomorphology by light and electron microscope. HAX1, ELANE, G6PC3, CSF3R, and JAGN1 mutations associated with SCN were studied in patients and several parents. Results: Significant increase in apoptosis and secondary necrosis in monocytes, lymphocytes, and granulocytes of the patients and parents was detected, irrespective of the mutation type. CD95 and CD95 ligand results implied that apoptosis was non-CD95-mediated. Leukocytes of 25%, 12.5%, and 0% of patients, parents, and controls showed rapid cell senescence. The cell cycle analysis testable in four cases showed G1 arrest and apoptosis in lymphocytes of three. The patients had HAX1 (n=6), ELANE (n=2), G6PC3 (n=2), and unidentified (n=5) mutations. The CD3, CD4, and NK lymphocytes were below normal levels in 16.6%, 8.3%, and 36.4% of the patients and in 0%, 0%, and 15.4% of the parents (controls: 0%, 0%, 5.6%). The thrombocytes aggregated at low rates, dense granule number/ thrombocyte ratio was low, and in vitro bleeding time was prolonged in 37.5%-66.6% of patients and 33.3%-63.2% of parents (vs. 0% in controls). Under electron and/or light microscope, the neutrophils, monocytes, lymphocytes, and thrombocytes in the peripheral blood of both patients and parents were dysplastic and the bone marrow of patients revealed increased phagocytic activity, dysmegakaryopoiesis, and necrotic and apoptotic cells. Ultrastructurally, thrombocyte adhesion, aggregation, and release were inadequate. Conclusion: In cases of SCN, patients’ pluripotent hematopoietic stem cells and their non-neutropenic parents are both affected irrespective of the genetic defect. © 2018 by Turkish Society of Hematology.en_US
dc.description.sponsorshipTürk Hematoloji Derneği, THD: 06-Ben_US
dc.description.sponsorshipThis project was supported by the Turkish Society of Hematology (Project No: 06-B). We would like to thank all the patients and their families for kindly participating in our study. We are grateful to Prof. Nejat Akar, Aysel Pekel MD, Prof. Birkayen_US
dc.identifier.doi10.4274/tjh.2017.0160en_US
dc.identifier.endpage259en_US
dc.identifier.issn1300-7777
dc.identifier.issue4en_US
dc.identifier.pmid30040071en_US
dc.identifier.scopus2-s2.0-85056297204en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage229en_US
dc.identifier.urihttps://doi.org/10.4274/tjh.2017.0160
dc.identifier.urihttps://hdl.handle.net/11454/70782
dc.identifier.volume35en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTurkish Society of Hematologyen_US
dc.relation.ispartofTurkish Journal of Hematologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectApoptosisen_US
dc.subjectFamilyen_US
dc.subjectLymphocytesen_US
dc.subjectMonocytesen_US
dc.subjectNK cellsen_US
dc.subjectParentsen_US
dc.subjectPhagocytesen_US
dc.subjectSenescenceen_US
dc.subjectSevere congenital neutropeniaen_US
dc.subjectThrombocytesen_US
dc.titleBoth granulocytic and non-granulocytic blood cells are affected in patients with severe congenital neutropenia and their non-neutropenic family members: An evaluation of morphology, function, and cell death [Ciddi konjenital nötropenisi olan hastalarda ve nötropenik olmayan ebeveynlerinde hem granülositik hem granülositik olmayan kan hücreleri etkilenir: Morfoloji, fonksiyon ve hücre ölümü yönünden bir değerlendirme]en_US
dc.typeArticleen_US

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