Storage Pool Disease of Platelets in an Infant with Thrombocytopenic Absent Radii (TAR) Syndrome Simulating Fanconi’s Anaemia

Zahavi, J.; Gale, RE; Kakkar, Vijay V.

doi:10.1159/000214396

Cited by 9 publications

(3 citation statements)

References 5 publications

(7 reference statements)

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“…TAR patients have low numbers of MKs in the BM that seem to have a maturation defect . In addition, there is some evidence that platelet function may be abnormal in these patients . Therefore, one might speculate that EVI1 regulation of RBM8A is crucial for late MK differentiation.…”

Section: Transcription Factors Implicated In Late Megakaryocyte Diffementioning

confidence: 99%

Transcription factors in late megakaryopoiesis and related platelet disorders

Tijssen

Ghevaert

2013

Journal of Thrombosis and Haemostasis

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Cell type-specific transcription factors regulate the repertoire of genes expressed in a cell and thereby determine its phenotype. The differentiation of megakaryocytes, the platelet progenitors, from hematopoietic stem cells is a well-known process that can be mimicked in culture. However, the efficient formation of platelets in culture remains a challenge. Platelet formation is a complicated process including megakaryocyte maturation, platelet assembly and platelet shedding. We hypothesize that a better understanding of the transcriptional regulation of this process will allow us to influence it such that sufficient numbers of platelets can be produced for clinical applications. After an introduction to gene regulation and platelet formation, this review summarizes the current knowledge of the regulation of platelet formation by the transcription factors EVI1, GATA1, FLI1, NFE2, RUNX1, SRF and its co-factor MKL1, and TAL1. Also covered is how some platelet disorders including myeloproliferative neoplasms, result from disturbances of the transcriptional regulation. These disorders give us invaluable insights into the crucial role these transcription factors play in platelet formation. Finally, there is discussion of how a better understanding of these processes will be needed to allow for efficient production of platelets in vitro.

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Section: Transcription Factors Implicated In Late Megakaryocyte Diffementioning

confidence: 99%

Transcription factors in late megakaryopoiesis and related platelet disorders

Tijssen

Ghevaert

2013

Journal of Thrombosis and Haemostasis

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“…TAR patients have low numbers of MKs in the BM, which seem to have a maturation defect [135]. In addition there is some evidence that platelet function may be abnormal in these patients [136][137][138]. Therefore, one might speculate that EVI1 regulation of RBM8A is crucial for late MK differentiation.…”

Section: Evi1mentioning

confidence: 99%

Transcriptional Regulation of Platelet Formation: Harnessing the Complexity for Efficient Platelet Production In Vitro

Tijssen

Moreau

Ghevaert

2016

Molecular and Cellular Biology of Platelet Formation

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It is now common knowledge that specific repertoires of transcription factors (TFs) determine a cell's protein content and thereby its phenotype. The expression of a given TF is not necessarily cell specific, and many TFs play a pivotal role in several different cell types. For example, TAL1, FLI1, RUNX1, ERG and GATA2 are important regulators of stem cells, but also play a vital role in megakaryopoiesis. Although the megakaryocyte (MK) and its closest relative, the red blood cell, share key TFs like GATA1 and NFE2, the bifurcation between the two lineages has been associated with pairs of TFs that act as a toggle switch (such as FLI1 and KLF1). This chapter will summarise the current knowledge of key transcriptional regulators of MK differentiation and how some of these TFs, despite being expressed in several cell types, can impose MK cell identity. Since the discovery of TPO in 1994, our knowledge of MK biology and differentiation has increased exponentially, but we still lack a deep understanding of what triggers the transition from MK growth and maturation to proplatelet formation. We describe how some well-known TFs control the expression of proteins that play a pivotal role in the dramatic cytoplasmic and cytoskeletal events that accompany proplatelet formation. Finally, we show how TFs can be harnessed in a powerful way to produce MKs and, potentially, platelets in vitro for future clinical applications.

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“…These disorders include gray platelet syndrome with decreased numbers to absence of alpha granules [ 3 , 4 ] and Hermansky-Pudlak syndrome [ 5 ], Chediak-Higashi syndrome [ 6 ], and Wiskott Aldrich syndrome [ 7 ] which are the best known conditions with absence or decreased numbers of dense granules. Additional dense granule deficiency disorders include Jacobsen/Paris Trousseau syndrome [ 8 ], thrombocytopenia with absent radius syndrome (TAR syndrome) [ 9 ], familial platelet disorder with RUNX1 mutations [ 10 ] that, and alpha-delta granule storage pool deficiency and white platelet syndrome that have decreased numbers of both alpha and dense granules) [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Medich Giant Platelet Syndrome: An Evolving Qualitative and Quantitative Platelet Disorder

et al. 2022

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Qualitative platelet disorders remain rare and varied. We describe here 2 additional patients with giant platelets, thrombocytopenia, deficiency in alpha granules and the presence of membranous inclusions within the cytoplasm. Collectively known as Medich syndrome, we further elucidated structural and clinical features of this rare syndrome. Platelets obtained from 2 patients with macro-thrombocytopenia were evaluated by electron microscopy. Structural findings were correlated with clinical characteristics. The defining morphologic feature found in the platelets of these patients is the presence of long, tubular inclusions consisting of several layers of membrane wrapped around a core of cytoplasm. These inclusions may deform the discoid shape of the platelet. In addition, abnormal giant alpha granules are present. Clinically all patients in the current report and review of the literature had mucosal bleeding and were often misdiagnosed as having immune related thrombocytopenia. To date five cases of Medich giant platelet syndrome have been reported. The cases are unified by the ultrastructural findings of abnormal alpha granules and unusual cytoplasmic scrolls. All patients experienced mucosal bleeding, however many clinical, biologic and genetic characteristics of this rare disorder remain to be determined.

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Storage Pool Disease of Platelets in an Infant with Thrombocytopenic Absent Radii (TAR) Syndrome Simulating Fanconi’s Anaemia

Cited by 9 publications

References 5 publications

Transcription factors in late megakaryopoiesis and related platelet disorders

Transcription factors in late megakaryopoiesis and related platelet disorders

Transcriptional Regulation of Platelet Formation: Harnessing the Complexity for Efficient Platelet Production In Vitro

Medich Giant Platelet Syndrome: An Evolving Qualitative and Quantitative Platelet Disorder

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