Longitudinal sequencing ofRUNX 1familial platelet disorder: new insights into genetic mechanisms of transformation to myeloid malignancies
| Autor: | Margareth C. Ozelo, Lucia H. Siqueira, Brooke Snetsinger, Gabriela G Yamaguti-Hayakawa, Michael J. Rauh, Samuel de Souza Medina, Fernando Ferreira Costa, Bruno Kosa Lino Duarte |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Neuroblastoma RAS viral oncogene homolog Myeloid Platelet disorder Buccal swab 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine hemic and lymphatic diseases medicine Humans Longitudinal Studies Germ-Line Mutation Myeloproliferative Disorders business.industry Myelodysplastic syndromes Hematology Middle Aged medicine.disease Haematopoiesis medicine.anatomical_structure RUNX1 chemistry 030220 oncology & carcinogenesis Core Binding Factor Alpha 2 Subunit Cancer research Female Blood Platelet Disorders Bone marrow business 030215 immunology |
| Zdroj: | British Journal of Haematology. 186:724-734 |
| ISSN: | 1365-2141 0007-1048 |
| Popis: | The mechanisms by which patients with RUNX1 familial platelet disorder with propensity to myeloid malignancies (FPDMM) develop myeloid malignancies (MM) are not fully understood. We report the results of targeted next-generation sequencing on three patients with RUNX1 FPDMM who developed acute myeloid leukaemia or myelodysplastic syndromes (AML/MDS). DNA samples were collected from bone marrow, peripheral blood and buccal swabs at different time points. One patient had clonal haematopoiesis, represented by an SRSF2 p.P95R variant, prior to his AML diagnosis, when he developed an additional NRAS p.G12D variant. His sister presented to us with MDS, with a TET2 p.S471fs and identical NRAS p.G12D variant. The third patient, from another family, had an additional RUNX1 p.R204X and an NFE2 p.Q139fs variant at AML diagnosis. This constitutes the first report of NFE2 variants in AML without extramedullary disease and NRAS variants in AML/MDS in the setting of FPDMM. A systematic review of the literature including our findings distinguishes two genetic landscapes at AML transformation from FPDMM characterized by either the presence or absence of somatic abnormalities in RUNX1 with or without variants in genes usually associated with MM. Whether clonal haematopoiesis precedes transformation only in patients without somatic abnormalities in RUNX1 needs further confirmation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text