Aggregates of nonmuscular myosin IIA in erythrocytes associate with GATA1- and GFI1B-related thrombocytopenia
Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved..
BACKGROUND: The transcription factor GATA1 is an essential regulator of erythroid cell gene expression and maturation and is also relevant for platelet biogenesis. GATA1-related thrombocytopenia (GATA1-RT) is a rare X-linked inherited platelet disorder (IPD) characterized by macrothrombocytopenia and dyserythropoiesis. Enlarged platelet size, reduced platelet granularity, and noticeable red blood cell anisopoikilocytosis are characteristic but unspecific morphological findings in GATA1-RT.
OBJECTIVES: To expand the investigation of platelet phenotype of patients with GATA1-RT by light- and immunofluorescence microscopy on a blood smear.
METHODS: We assessed blood smears by light- and immunofluorescence microscopy after May-Grünwald Giemsa staining using a set of 13 primary antibodies against markers belonging to different platelet structures. Antibody binding was visualized by fluorescently labeled secondary antibodies.
RESULTS: We investigated 12 individuals with genetically confirmed GATA1-RT from 8 unrelated families. While confirming the already known characteristic of platelet morphology (platelet macrocytosis and reduced expression of markers for α-granules), we also found aggregates of nonmuscular myosin heavy chain II A (NMMIIA) in the erythrocytes in all individuals (1-3 aggregates/cell, 1-3 μm diameter). By systematically reanalyzing blood smears from a cohort of patients with 19 different forms of IPD, we found similar NMMIIA aggregates in the red blood cells only in subjects with GFI1B-related thrombocytopenia (GFI1B-RT), the other major IPD featured by dyserythropoiesis.
CONCLUSION: Aggregates of NMMIIA in the erythrocytes associate with GATA1-RT and GFI1B-RT and can facilitate their diagnosis on blood smears. This previously unreported finding might represent a novel marker of dyserythropoiesis assessable in peripheral blood.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Journal of thrombosis and haemostasis : JTH - 22(2024), 4 vom: 23. März, Seite 1179-1186 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zaninetti, Carlo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 26.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jtha.2023.12.007 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Zaninetti, Carlo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Aggregates of nonmuscular myosin IIA in erythrocytes associate with GATA1- and GFI1B-related thrombocytopenia |
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| 500 | |a Date Revised 26.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: The transcription factor GATA1 is an essential regulator of erythroid cell gene expression and maturation and is also relevant for platelet biogenesis. GATA1-related thrombocytopenia (GATA1-RT) is a rare X-linked inherited platelet disorder (IPD) characterized by macrothrombocytopenia and dyserythropoiesis. Enlarged platelet size, reduced platelet granularity, and noticeable red blood cell anisopoikilocytosis are characteristic but unspecific morphological findings in GATA1-RT | ||
| 520 | |a OBJECTIVES: To expand the investigation of platelet phenotype of patients with GATA1-RT by light- and immunofluorescence microscopy on a blood smear | ||
| 520 | |a METHODS: We assessed blood smears by light- and immunofluorescence microscopy after May-Grünwald Giemsa staining using a set of 13 primary antibodies against markers belonging to different platelet structures. Antibody binding was visualized by fluorescently labeled secondary antibodies | ||
| 520 | |a RESULTS: We investigated 12 individuals with genetically confirmed GATA1-RT from 8 unrelated families. While confirming the already known characteristic of platelet morphology (platelet macrocytosis and reduced expression of markers for α-granules), we also found aggregates of nonmuscular myosin heavy chain II A (NMMIIA) in the erythrocytes in all individuals (1-3 aggregates/cell, 1-3 μm diameter). By systematically reanalyzing blood smears from a cohort of patients with 19 different forms of IPD, we found similar NMMIIA aggregates in the red blood cells only in subjects with GFI1B-related thrombocytopenia (GFI1B-RT), the other major IPD featured by dyserythropoiesis | ||
| 520 | |a CONCLUSION: Aggregates of NMMIIA in the erythrocytes associate with GATA1-RT and GFI1B-RT and can facilitate their diagnosis on blood smears. This previously unreported finding might represent a novel marker of dyserythropoiesis assessable in peripheral blood | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a GATA1 Transcription Factor |2 NLM | |
| 650 | 7 | |a GFI1B protein, human |2 NLM | |
| 650 | 7 | |a Nonmuscle Myosin Type IIA |2 NLM | |
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| 650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
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| 700 | 1 | |a Rivera, Jose' |e verfasserin |4 aut | |
| 700 | 1 | |a Vater, Leonard |e verfasserin |4 aut | |
| 700 | 1 | |a Ohlenforst, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Leinøe, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Böckelmann, Doris |e verfasserin |4 aut | |
| 700 | 1 | |a Freson, Kathleen |e verfasserin |4 aut | |
| 700 | 1 | |a Thiele, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Makhloufi, Houssain |e verfasserin |4 aut | |
| 700 | 1 | |a Rath, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Eberl, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a Wolff, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Freyer, Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Wesche, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Zieger, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Felbor, Ute |e verfasserin |4 aut | |
| 700 | 1 | |a Heidel, Florian H |e verfasserin |4 aut | |
| 700 | 1 | |a Greinacher, Andreas |e verfasserin |4 aut | |
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