A germline FLT3 variant in aplastic anemia
Abstract FMS-like tyrosine kinase 3 (FLT3) genetic variants are commonly seen in high-grade myeloid neoplasms and are typically gain-of-function mutations associated with a proliferative disease phenotype. Inactivating FLT3 variants have been less frequently described in non-malignant, autoimmune di...
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BMC
2025-01-01
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| Series: | Biomarker Research |
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| Online Access: | https://doi.org/10.1186/s40364-024-00717-3 |
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| author | Lemchukwu C. Amaeshi Amalia A. Sofianidi Aditi Shastri Mendel Goldfinger Marina Konopleva Amit K. Verma Mark Chaitowitz Ioannis Mantzaris |
| author_facet | Lemchukwu C. Amaeshi Amalia A. Sofianidi Aditi Shastri Mendel Goldfinger Marina Konopleva Amit K. Verma Mark Chaitowitz Ioannis Mantzaris |
| author_sort | Lemchukwu C. Amaeshi |
| collection | DOAJ |
| description | Abstract FMS-like tyrosine kinase 3 (FLT3) genetic variants are commonly seen in high-grade myeloid neoplasms and are typically gain-of-function mutations associated with a proliferative disease phenotype. Inactivating FLT3 variants have been less frequently described in non-malignant, autoimmune disorders and are uncommon in aplastic anemia (AA). Herein, we report the first to our knowledge, and unusual case of a germline, gain-of-function, FLT3 variant in a patient with severe AA treated successfully with immunosuppressive therapy. Although a proposed link between dysregulated FLT3 signaling and autoimmunity has been described and could be speculated in the case of AA, it is currently unknown whether a pathogenetic connection between an activating germline FLT3 variant and AA truly exists and whether the mutation signifies a lifelong risk of disease recurrence and/or clonal evolution. However, the recognition of the FLT3 gene as subject not only to somatic but also germline mutations is the first step in interrogating its functional implications. Further study of unusual genotype-phenotype combinations, such as in the case presented, may shed light on a potential pathogenetic link. |
| format | Article |
| id | doaj-art-813015e84cbe4d01a9f77bf7ebdc8d74 |
| institution | Kabale University |
| issn | 2050-7771 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj-art-813015e84cbe4d01a9f77bf7ebdc8d742025-01-12T12:33:47ZengBMCBiomarker Research2050-77712025-01-011311410.1186/s40364-024-00717-3A germline FLT3 variant in aplastic anemiaLemchukwu C. Amaeshi0Amalia A. Sofianidi1Aditi Shastri2Mendel Goldfinger3Marina Konopleva4Amit K. Verma5Mark Chaitowitz6Ioannis Mantzaris7Montefiore Medical CenterDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of AthensDepartment of Oncology, Montefiore Medical Center and Albert Einstein College of MedicineDepartment of Oncology, Montefiore Medical Center and Albert Einstein College of MedicineDepartment of Oncology, Montefiore Medical Center and Albert Einstein College of MedicineDepartment of Oncology, Montefiore Medical Center and Albert Einstein College of MedicineDepartment of Oncology, Montefiore Medical Center and Albert Einstein College of MedicineDepartment of Oncology, Montefiore Medical Center and Albert Einstein College of MedicineAbstract FMS-like tyrosine kinase 3 (FLT3) genetic variants are commonly seen in high-grade myeloid neoplasms and are typically gain-of-function mutations associated with a proliferative disease phenotype. Inactivating FLT3 variants have been less frequently described in non-malignant, autoimmune disorders and are uncommon in aplastic anemia (AA). Herein, we report the first to our knowledge, and unusual case of a germline, gain-of-function, FLT3 variant in a patient with severe AA treated successfully with immunosuppressive therapy. Although a proposed link between dysregulated FLT3 signaling and autoimmunity has been described and could be speculated in the case of AA, it is currently unknown whether a pathogenetic connection between an activating germline FLT3 variant and AA truly exists and whether the mutation signifies a lifelong risk of disease recurrence and/or clonal evolution. However, the recognition of the FLT3 gene as subject not only to somatic but also germline mutations is the first step in interrogating its functional implications. Further study of unusual genotype-phenotype combinations, such as in the case presented, may shed light on a potential pathogenetic link.https://doi.org/10.1186/s40364-024-00717-3Aplastic anemiaFLT3 variantGermline variantPancytopeniaAutoimmunityDendritic cells |
| spellingShingle | Lemchukwu C. Amaeshi Amalia A. Sofianidi Aditi Shastri Mendel Goldfinger Marina Konopleva Amit K. Verma Mark Chaitowitz Ioannis Mantzaris A germline FLT3 variant in aplastic anemia Biomarker Research Aplastic anemia FLT3 variant Germline variant Pancytopenia Autoimmunity Dendritic cells |
| title | A germline FLT3 variant in aplastic anemia |
| title_full | A germline FLT3 variant in aplastic anemia |
| title_fullStr | A germline FLT3 variant in aplastic anemia |
| title_full_unstemmed | A germline FLT3 variant in aplastic anemia |
| title_short | A germline FLT3 variant in aplastic anemia |
| title_sort | germline flt3 variant in aplastic anemia |
| topic | Aplastic anemia FLT3 variant Germline variant Pancytopenia Autoimmunity Dendritic cells |
| url | https://doi.org/10.1186/s40364-024-00717-3 |
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