The study of genetic mutations that influences thrombopoiesis in patients with myelodysplasia: the roles of Ankrd26, Runx-1 and Etv6
(Abstract release date: 05/19/16)
EHA Library. Fabris F. 06/09/16; 132962; E1413
Fabrizio Fabris
Contributions
Contributions
Abstract
Abstract: E1413
Type: Eposter Presentation
Background
The phenotype of inherited thrombocytopenia is characterized by different sizes of platelets, different degrees of thrombocytopenia, the presence or absence of platelet function defects, and an association with syndromes involving other cell lines or other organ functions. In particular, some forms of inherited thrombocytopenia secondary to 5’ UTR of ANKRD26, RUNX-1, and ETV6 mutations are associated with neoplasms of haematological or non-haematological type.
Aims
Study of genetic mutations in ANKRD26, RUNX-1 and ETV6 that influences thrombopoiesis in patients with myelodysplasia (MDS).
Methods
We study the presence of mutations in the 5’UTR of the ANKRD26, RUNX-1, and ETV6 gene in the following cohorts of patients: a) 27 patients affected by sporadic and familial thrombocytopenia and normal platelet volumes, b) 12 patients with myelodysplasia and normal platelet count, c) 9 patients with myelodysplasia with prevalent thrombocytopenia.
Results
In the cohort of the studied patients we found mutations in the 5’UTR of the ANKRD26, RUNX-1 and ETV6 genes only in 6 patients with thrombocytopenia and MDS of the group c. The mutations found are 5. One deletion in exon 1 of the ANKRD26 gene (c.60_62del AGA), three mutations in the RUNX-1 gene: a missense mutation with a modification in the amino acid polarity in exon 4 (c.76C>G), a deletion (c.934del A) and an insertion (c.1214_1215insTG), respectively, in exon 8 and 9. Finally, a deletion in intron 1 of the ETV6 gene (c.28+192delC). All the mutations found were not present in public databases.
Conclusion
The preliminary data demonstrated that mutations in the ANKRD26, RUNX-1 and ETV6 genes were present in patients with MDS and prevalent thrombocytopenia. Even if the involvement of these genes in megacaryopoiesis is well known, the exact mechanism responsible for thrombocytopenia is not yet clear. As the pathology is extremely rare, it is difficult to find data for genotype-phenotype analyses. However we hypothesized that these mutations are responsible for the low platelet counts in patients with myelodysplasia. Greater knowledge about the pathogenesis of these forms of thrombocytopenia will facilitate finding new therapies for them. This will have important clinical implications since platelet transfusion is the only therapeutic option for these patients. Defining the molecular mechanism of thrombocytopenia in these patients could constitute the first step on the path leading to new therapeutic possibilities with TPO mimetics as has been demonstrated in hereditary form of thrombocytopenia.
Session topic: E-poster
Keyword(s): Genetic, Platelet, Thrombocytopenia
Type: Eposter Presentation
Background
The phenotype of inherited thrombocytopenia is characterized by different sizes of platelets, different degrees of thrombocytopenia, the presence or absence of platelet function defects, and an association with syndromes involving other cell lines or other organ functions. In particular, some forms of inherited thrombocytopenia secondary to 5’ UTR of ANKRD26, RUNX-1, and ETV6 mutations are associated with neoplasms of haematological or non-haematological type.
Aims
Study of genetic mutations in ANKRD26, RUNX-1 and ETV6 that influences thrombopoiesis in patients with myelodysplasia (MDS).
Methods
We study the presence of mutations in the 5’UTR of the ANKRD26, RUNX-1, and ETV6 gene in the following cohorts of patients: a) 27 patients affected by sporadic and familial thrombocytopenia and normal platelet volumes, b) 12 patients with myelodysplasia and normal platelet count, c) 9 patients with myelodysplasia with prevalent thrombocytopenia.
Results
In the cohort of the studied patients we found mutations in the 5’UTR of the ANKRD26, RUNX-1 and ETV6 genes only in 6 patients with thrombocytopenia and MDS of the group c. The mutations found are 5. One deletion in exon 1 of the ANKRD26 gene (c.60_62del AGA), three mutations in the RUNX-1 gene: a missense mutation with a modification in the amino acid polarity in exon 4 (c.76C>G), a deletion (c.934del A) and an insertion (c.1214_1215insTG), respectively, in exon 8 and 9. Finally, a deletion in intron 1 of the ETV6 gene (c.28+192delC). All the mutations found were not present in public databases.
Conclusion
The preliminary data demonstrated that mutations in the ANKRD26, RUNX-1 and ETV6 genes were present in patients with MDS and prevalent thrombocytopenia. Even if the involvement of these genes in megacaryopoiesis is well known, the exact mechanism responsible for thrombocytopenia is not yet clear. As the pathology is extremely rare, it is difficult to find data for genotype-phenotype analyses. However we hypothesized that these mutations are responsible for the low platelet counts in patients with myelodysplasia. Greater knowledge about the pathogenesis of these forms of thrombocytopenia will facilitate finding new therapies for them. This will have important clinical implications since platelet transfusion is the only therapeutic option for these patients. Defining the molecular mechanism of thrombocytopenia in these patients could constitute the first step on the path leading to new therapeutic possibilities with TPO mimetics as has been demonstrated in hereditary form of thrombocytopenia.
Session topic: E-poster
Keyword(s): Genetic, Platelet, Thrombocytopenia
Abstract: E1413
Type: Eposter Presentation
Background
The phenotype of inherited thrombocytopenia is characterized by different sizes of platelets, different degrees of thrombocytopenia, the presence or absence of platelet function defects, and an association with syndromes involving other cell lines or other organ functions. In particular, some forms of inherited thrombocytopenia secondary to 5’ UTR of ANKRD26, RUNX-1, and ETV6 mutations are associated with neoplasms of haematological or non-haematological type.
Aims
Study of genetic mutations in ANKRD26, RUNX-1 and ETV6 that influences thrombopoiesis in patients with myelodysplasia (MDS).
Methods
We study the presence of mutations in the 5’UTR of the ANKRD26, RUNX-1, and ETV6 gene in the following cohorts of patients: a) 27 patients affected by sporadic and familial thrombocytopenia and normal platelet volumes, b) 12 patients with myelodysplasia and normal platelet count, c) 9 patients with myelodysplasia with prevalent thrombocytopenia.
Results
In the cohort of the studied patients we found mutations in the 5’UTR of the ANKRD26, RUNX-1 and ETV6 genes only in 6 patients with thrombocytopenia and MDS of the group c. The mutations found are 5. One deletion in exon 1 of the ANKRD26 gene (c.60_62del AGA), three mutations in the RUNX-1 gene: a missense mutation with a modification in the amino acid polarity in exon 4 (c.76C>G), a deletion (c.934del A) and an insertion (c.1214_1215insTG), respectively, in exon 8 and 9. Finally, a deletion in intron 1 of the ETV6 gene (c.28+192delC). All the mutations found were not present in public databases.
Conclusion
The preliminary data demonstrated that mutations in the ANKRD26, RUNX-1 and ETV6 genes were present in patients with MDS and prevalent thrombocytopenia. Even if the involvement of these genes in megacaryopoiesis is well known, the exact mechanism responsible for thrombocytopenia is not yet clear. As the pathology is extremely rare, it is difficult to find data for genotype-phenotype analyses. However we hypothesized that these mutations are responsible for the low platelet counts in patients with myelodysplasia. Greater knowledge about the pathogenesis of these forms of thrombocytopenia will facilitate finding new therapies for them. This will have important clinical implications since platelet transfusion is the only therapeutic option for these patients. Defining the molecular mechanism of thrombocytopenia in these patients could constitute the first step on the path leading to new therapeutic possibilities with TPO mimetics as has been demonstrated in hereditary form of thrombocytopenia.
Session topic: E-poster
Keyword(s): Genetic, Platelet, Thrombocytopenia
Type: Eposter Presentation
Background
The phenotype of inherited thrombocytopenia is characterized by different sizes of platelets, different degrees of thrombocytopenia, the presence or absence of platelet function defects, and an association with syndromes involving other cell lines or other organ functions. In particular, some forms of inherited thrombocytopenia secondary to 5’ UTR of ANKRD26, RUNX-1, and ETV6 mutations are associated with neoplasms of haematological or non-haematological type.
Aims
Study of genetic mutations in ANKRD26, RUNX-1 and ETV6 that influences thrombopoiesis in patients with myelodysplasia (MDS).
Methods
We study the presence of mutations in the 5’UTR of the ANKRD26, RUNX-1, and ETV6 gene in the following cohorts of patients: a) 27 patients affected by sporadic and familial thrombocytopenia and normal platelet volumes, b) 12 patients with myelodysplasia and normal platelet count, c) 9 patients with myelodysplasia with prevalent thrombocytopenia.
Results
In the cohort of the studied patients we found mutations in the 5’UTR of the ANKRD26, RUNX-1 and ETV6 genes only in 6 patients with thrombocytopenia and MDS of the group c. The mutations found are 5. One deletion in exon 1 of the ANKRD26 gene (c.60_62del AGA), three mutations in the RUNX-1 gene: a missense mutation with a modification in the amino acid polarity in exon 4 (c.76C>G), a deletion (c.934del A) and an insertion (c.1214_1215insTG), respectively, in exon 8 and 9. Finally, a deletion in intron 1 of the ETV6 gene (c.28+192delC). All the mutations found were not present in public databases.
Conclusion
The preliminary data demonstrated that mutations in the ANKRD26, RUNX-1 and ETV6 genes were present in patients with MDS and prevalent thrombocytopenia. Even if the involvement of these genes in megacaryopoiesis is well known, the exact mechanism responsible for thrombocytopenia is not yet clear. As the pathology is extremely rare, it is difficult to find data for genotype-phenotype analyses. However we hypothesized that these mutations are responsible for the low platelet counts in patients with myelodysplasia. Greater knowledge about the pathogenesis of these forms of thrombocytopenia will facilitate finding new therapies for them. This will have important clinical implications since platelet transfusion is the only therapeutic option for these patients. Defining the molecular mechanism of thrombocytopenia in these patients could constitute the first step on the path leading to new therapeutic possibilities with TPO mimetics as has been demonstrated in hereditary form of thrombocytopenia.
Session topic: E-poster
Keyword(s): Genetic, Platelet, Thrombocytopenia
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