ETV6-related thrombocytopenia and platelet dysfunction

Paola, Jorge Di; Fisher, Marlie H

doi:10.1080/09537104.2020.1760229

Cited by 4 publications

(7 citation statements)

References 23 publications

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“…The WHO’s 2016 revision of the classification of myeloid neoplasms and acute leukemias [ 155 ] introduced a new category of diseases defined as myeloid neoplasms with germline predisposition and pre-existing platelet disorders, that includes those that evolve with molecular variants on ankyrin repeat domain 26 gene ( ANKRD26 ) or on transcription factors ETV6 and RUNX1 [ 18 , 19 , 20 , 22 , 122 , 156 , 157 ].…”

Section: Inherited Platelet Disorders Of Particular Clinical Relevancementioning

confidence: 99%

“…Likewise, many of these IPD comprise part of multisystemic disorders known as syndromic IPD. In some, bleeding may be clinically irrelevant, but patients display or are at high risk of presenting relevant disorders of other organs or tissues, or even neoplasms [ 1 , 5 , 7 , 121 , 122 ] ( Table 1 , Table 3 and Table 4 ). A relationship between genotype (the gene and type of molecular defect) and prognosis and/or clinical severity has been established in some IPD, making a molecular diagnosis especially imperative to guide clinical management [ 2 , 123 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inherited Platelet Disorders: An Updated Overview

Palma-Barqueros

Revilla

Sánchez

et al. 2021

IJMS

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Platelets play a major role in hemostasis as ppwell as in many other physiological and pathological processes. Accordingly, production of about 1011 platelet per day as well as appropriate survival and functions are life essential events. Inherited platelet disorders (IPDs), affecting either platelet count or platelet functions, comprise a heterogenous group of about sixty rare diseases caused by molecular anomalies in many culprit genes. Their clinical relevance is highly variable according to the specific disease and even within the same type, ranging from almost negligible to life-threatening. Mucocutaneous bleeding diathesis (epistaxis, gum bleeding, purpura, menorrhagia), but also multisystemic disorders and/or malignancy comprise the clinical spectrum of IPDs. The early and accurate diagnosis of IPDs and a close patient medical follow-up is of great importance. A genotype–phenotype relationship in many IPDs makes a molecular diagnosis especially relevant to proper clinical management. Genetic diagnosis of IPDs has been greatly facilitated by the introduction of high throughput sequencing (HTS) techniques into mainstream investigation practice in these diseases. However, there are still unsolved ethical concerns on general genetic investigations. Patients should be informed and comprehend the potential implications of their genetic analysis. Unlike the progress in diagnosis, there have been no major advances in the clinical management of IPDs. Educational and preventive measures, few hemostatic drugs, platelet transfusions, thrombopoietin receptor agonists, and in life-threatening IPDs, allogeneic hematopoietic stem cell transplantation are therapeutic possibilities. Gene therapy may be a future option. Regular follow-up by a specialized hematology service with multidisciplinary support especially for syndromic IPDs is mandatory.

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Section: Inherited Platelet Disorders Of Particular Clinical Relevancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inherited Platelet Disorders: An Updated Overview

Palma-Barqueros

Revilla

Sánchez

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…Typical platelet counts in patients with ETV6 ‐RT are in the mild to moderate thrombocytopenia range, usually >75 × 10 9 /L 4,5 . Platelet size is normal, and platelet morphology or peripheral smear findings do not show distinguishing features that set it apart from other inherited thrombocytopenias 3,5 . Mean corpuscular volume can be mildly elevated in patients with ETV6 ‐RT, 4,6 and while not specific to this disorder, is a useful clinical clue when present.…”

Section: Discussionmentioning

confidence: 99%

“…Over 50 genes have been described to be associated with inherited thrombocytopenia and an estimated 2.7% are from disease‐causing variants in ETS Variant Transcription Factor 6 ( ETV6 ) 1,2 . ETV6 is a transcription repressor in the ETS family of transcription factors, and it is implicated in normal hematopoiesis, thrombopoiesis, and platelet function 3,4 . Distinguishing ETV6 ‐related thrombocytopenia ( ETV6 ‐RT) from other etiologies is important, given its associated risk of malignancy, 2–4 and requires genetic testing for diagnostic confirmation.…”

Section: Introductionmentioning

confidence: 99%

More than just mild thrombocytopenia: Clinical clues in the diagnosis of germline predisposition to malignancy from a rare ETV6 variant

Fang

Botero

Hackney

2023

Clinical Case Reports

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Thrombocytopenia can be the first indication of an underlying condition in children and includes a wide range of differential diagnoses. Inherited thrombocytopenias are a heterogenous group of disorders with low platelet counts, with or without platelet dysfunction. With increasing access to genetic testing, the number of genes associated with this phenotype and number of patients diagnosed continue to grow. 1 Over 50 genes have been described to be associated with inherited thrombocytopenia and an estimated 2.7% are from disease-causing variants in ETS Variant Transcription Factor 6 (ETV6). 1,2 ETV6 is a transcription repressor in the ETS family of transcription factors, and it is implicated in normal hematopoiesis, thrombopoiesis, and platelet function. 3,4 Distinguishing ETV6-related thrombocytopenia (ETV6-RT) from other etiologies is important, given its associated risk of malignancy, 2-4 and requires genetic testing for diagnostic confirmation. This report describes the diagnostic approach and clinical challenges in a family with inherited thrombocytopenia that was found to carry a rare disease-causing ETV6 variant.

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“…ETV6 protein is a transcriptional repressor encoded by the ETS variant 6 ( ETV6 ) gene (formerly known as the TEL gene) located on chromosome 12p13. Hotspot mutations are mainly missense and located on the DNA-binding site (ETS domain) 45–47 . Germline ETV6 mutations ( ETV6 mut ) are inherited in an AD fashion and generate a dominant negative effect by preventing wild-type ETV6 protein from entering the nucleus, eventually leading to reduced transcriptional repression and megakaryocyte maturation arrest 47,48 …”

Section: Myeloid Neoplasms With Germline Predisposition and A Preexis...mentioning

confidence: 99%

Germline Predisposition to Myelodysplastic Syndromes

Gener-Ricos¹,

Gerstein

Hammond³

et al. 2023

Cancer J

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While germline predisposition to myelodysplastic syndromes is well-established, knowledge has advanced rapidly resulting in more cases of inherited hematologic malignancies being identified. Understanding the biological features and main clinical manifestations of hereditary hematologic malignancies is essential to recognizing and referring patients with myelodysplastic syndrome, who may underlie inherited predisposition, for appropriate genetic evaluation. Importance lies in individualized genetic counseling along with informed treatment decisions, especially with regard to hematopoietic stem cell transplant–related donor selection. Future studies will improve comprehension of these disorders, enabling better management of affected patients and their families.

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ETV6-related thrombocytopenia and platelet dysfunction

Cited by 4 publications

References 23 publications

Inherited Platelet Disorders: An Updated Overview

Inherited Platelet Disorders: An Updated Overview

More than just mild thrombocytopenia: Clinical clues in the diagnosis of germline predisposition to malignancy from a rare ETV6 variant

Germline Predisposition to Myelodysplastic Syndromes

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