Germline ETV6 mutations and predisposition to hematological malignancies

Feurstein, Simone; Godley, Lucy A.

doi:10.1007/s12185-017-2259-4

Cited by 67 publications

(41 citation statements)

References 43 publications

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“…This uniform AML phenotype differs from the diverse hematologic malignancies seen in GATA-2 deficiency syndrome, FPDMM, and THC5, and parallels the more lineage-restricted phenotypes of C/ sense mutations within the C-terminal DNA-binding domain ( Table 4) (149)(150)(151)(152)(153). One linker region mutation, p.P214L, is also recurrent (152,154). Rare truncating or missense mutations outside the DNA-binding and linker domains have been reported.…”

Section: Thrombocytopenia 5 (Thc5)mentioning

confidence: 64%

Transcription factor mutations as a cause of familial myeloid neoplasms

Churpek¹,

Bresnick²

2019

Journal of Clinical Investigation

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Section: Thrombocytopenia 5 (Thc5)mentioning

confidence: 64%

Transcription factor mutations as a cause of familial myeloid neoplasms

Churpek¹,

Bresnick²

2019

Journal of Clinical Investigation

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“…ETV6 has eight exons encoding for three functional domains: a highly conserved C‐terminal ETS domain which mediates sequence‐specific binding of target DNA; a central regulatory domain; and another highly conserved N‐terminal PNT domain which mediates homo‐oligomerization and is required for nuclear localization of the protein. ETV6 acts as a transcriptional repressor that is regulated by autoinhibition and homodimerization . It inhibits the activity of other ETS domain containing transcription factors critical in megakaryocyte development like FLI1 …”

Section: Myeloid Neoplasms With Germline Etv6 Mutationmentioning

confidence: 99%

“…ETV6 ‐RT is a highly penetrant form of IT with autosomal dominant mode of inheritance. Patients usually present with mild‐to‐moderate thrombocytopenia with platelet counts ranging from 29 to 118 x 10 9 /L . Severe thrombocytopenia is rare .…”

Section: Myeloid Neoplasms With Germline Etv6 Mutationmentioning

confidence: 99%

“…ETV6-RTand its association with hematological malignancies were initially described in early 2015 by Zhang et al 77 repressor that is regulated by autoinhibition and homodimerization. 83 It inhibits the activity of other ETS domain containing transcription factors critical in megakaryocyte development like FLI1. 84,85 It has been shown ETV6 knockout mice die between embryonic day 10.5-11.5 secondary to defective yolk sac angiogenesis.…”

Section: Early Descriptionmentioning

confidence: 99%

“…Patients usually present with mild-to-moderate thrombocytopenia with platelet counts ranging from 29 to 118 x 10 9 /L. 83,94 Severe thrombocytopenia is rare. 94 A subset of patients presents with mild-to-moderate bleeding symptoms, commonly petechiae, ecchymoses, gum bleeding, epistaxis, and menorrhagia.…”

Section: Clinical Presentationmentioning

confidence: 99%

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Inherited thrombocytopenia and platelet disorders with germline predisposition to myeloid neoplasia

Galera

Dulau‐Florea

Calvo

2019

Int J Lab Hematology

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Advances in molecular genetic sequencing techniques have contributed to the elucidation of previously unknown germline mutations responsible for inherited thrombocytopenia (IT). Regardless of age of presentation and severity of symptoms related to thrombocytopenia and/or platelet dysfunction, a subset of patients with IT are at increased risk of developing myeloid neoplasms during their life time, particularly those with germline autosomal dominant mutations in RUNX1, ANKRD26, and ETV6. Patients may present with isolated thrombocytopenia and megakaryocytic dysmorphia or atypia on baseline bone marrow evaluation, without constituting myelodysplasia (MDS). Bone marrow features may overlap with idiopathic thrombocytopenic purpura (ITP) or sporadic MDS leading to misdiagnosis. Progression to myelodysplastic syndrome/ acute myeloid leukemia (MDS/AML) may be accompanied by progressive bi‐ or pancytopenia, multilineage dysplasia, increased blasts, cytogenetic abnormalities, acquisition of bi‐allelic mutations in the underlying gene with germline mutation, or additional somatic mutations in genes associated with myeloid malignancy. A subset of patients may present with MDS/AML at a young age, underscoring the growing concern for evaluating young patients with MDS/AML for germline mutations predisposing to myeloid neoplasm. Early recognition of germline mutation and predisposition to myeloid malignancy permits appropriate treatment, adequate monitoring for disease progression, proper donor selection for hematopoietic stem cell transplantation, as well as genetic counseling of the affected patients and their family members. Herein, we describe the clinical and diagnostic features of IT with germline mutations predisposing to myeloid neoplasms focusing on mutations involving RUNX1, ANKRD26, and ETV6.

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2021

Constitutional Oncogenetics

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Germline ETV6 mutations and predisposition to hematological malignancies

Cited by 67 publications

References 43 publications

Transcription factor mutations as a cause of familial myeloid neoplasms

Transcription factor mutations as a cause of familial myeloid neoplasms

Inherited thrombocytopenia and platelet disorders with germline predisposition to myeloid neoplasia

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