ETV6-related thrombocytopenia and platelet dysfunction
We and others recently described families with germline heterozygote mutations in ETV6 leading to autosomal dominant highly penetrant thrombocytopenia, red cell macrocytosis and predisposition to leukemia.The bone marrow of affected individuals shows erythroid dysplasia and hyperplasia of small, hyp...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2020.1760229 |
| _version_ | 1797684190467063808 |
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| author | Jorge Di Paola Marlie H. Fisher |
| author_facet | Jorge Di Paola Marlie H. Fisher |
| author_sort | Jorge Di Paola |
| collection | DOAJ |
| description | We and others recently described families with germline heterozygote mutations in ETV6 leading to autosomal dominant highly penetrant thrombocytopenia, red cell macrocytosis and predisposition to leukemia.The bone marrow of affected individuals shows erythroid dysplasia and hyperplasia of small, hypolobulated immature megakaryocytes suggesting a differentiation arrest. This discovery led to subsequent studies that confirmed our findings and to additional larger studies that demonstrated a 1% frequency of germline ETV6 mutations among 4405 individuals with acute lymphoblastic leukemia. Additionally, a 4.5% prevalence of ETV6 germline mutations was reported in families with inherited thrombocytopenia. Preliminary data suggest that decreased ETV6 function leads to MK maturation arrest, impaired platelet production and differentially expressed platelet transcripts among individuals affected with ETV6 mutations when compared to control relatives. Additionally, individuals with some ETV6 mutation exhibit bleeding that appears disproportionate to the mildly reduced platelet count, suggesting a platelet function deficit. Furthermore, recent studies describe decreased ability of platelets from individuals with ETV6 mutations to spread on fibrinogen covered surfaces. Overall, ETV6 germline mutations represent a new cancer predisposition thrombocytopenia with platelet dysfunction. |
| first_indexed | 2024-03-12T00:26:01Z |
| format | Article |
| id | doaj.art-311fddb4a86d46798f5e56c78a5231dc |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:26:01Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-311fddb4a86d46798f5e56c78a5231dc2023-09-15T10:38:07ZengTaylor & Francis GroupPlatelets0953-71041369-16352021-01-0132114114310.1080/09537104.2020.17602291760229ETV6-related thrombocytopenia and platelet dysfunctionJorge Di Paola0Marlie H. Fisher1Washington University School of Medicine in St. LouisUniversity of Colorado Anschutz Medical CampusWe and others recently described families with germline heterozygote mutations in ETV6 leading to autosomal dominant highly penetrant thrombocytopenia, red cell macrocytosis and predisposition to leukemia.The bone marrow of affected individuals shows erythroid dysplasia and hyperplasia of small, hypolobulated immature megakaryocytes suggesting a differentiation arrest. This discovery led to subsequent studies that confirmed our findings and to additional larger studies that demonstrated a 1% frequency of germline ETV6 mutations among 4405 individuals with acute lymphoblastic leukemia. Additionally, a 4.5% prevalence of ETV6 germline mutations was reported in families with inherited thrombocytopenia. Preliminary data suggest that decreased ETV6 function leads to MK maturation arrest, impaired platelet production and differentially expressed platelet transcripts among individuals affected with ETV6 mutations when compared to control relatives. Additionally, individuals with some ETV6 mutation exhibit bleeding that appears disproportionate to the mildly reduced platelet count, suggesting a platelet function deficit. Furthermore, recent studies describe decreased ability of platelets from individuals with ETV6 mutations to spread on fibrinogen covered surfaces. Overall, ETV6 germline mutations represent a new cancer predisposition thrombocytopenia with platelet dysfunction.http://dx.doi.org/10.1080/09537104.2020.1760229bleedingetv6thrombocytopenia |
| spellingShingle | Jorge Di Paola Marlie H. Fisher ETV6-related thrombocytopenia and platelet dysfunction Platelets bleeding etv6 thrombocytopenia |
| title | ETV6-related thrombocytopenia and platelet dysfunction |
| title_full | ETV6-related thrombocytopenia and platelet dysfunction |
| title_fullStr | ETV6-related thrombocytopenia and platelet dysfunction |
| title_full_unstemmed | ETV6-related thrombocytopenia and platelet dysfunction |
| title_short | ETV6-related thrombocytopenia and platelet dysfunction |
| title_sort | etv6 related thrombocytopenia and platelet dysfunction |
| topic | bleeding etv6 thrombocytopenia |
| url | http://dx.doi.org/10.1080/09537104.2020.1760229 |
| work_keys_str_mv | AT jorgedipaola etv6relatedthrombocytopeniaandplateletdysfunction AT marliehfisher etv6relatedthrombocytopeniaandplateletdysfunction |