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Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies
Pediatric myelodysplastic syndromes (MDS) often raise concern for an underlying germline predisposition to hematologic malignancies, referred to as germline predisposition herein. With the availability of genetic testing, it is now clear that syndromic features may be lacking in patients with germli...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959480/ https://www.ncbi.nlm.nih.gov/pubmed/35356204 http://dx.doi.org/10.3389/fonc.2022.813149 |
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author | Avagyan, Serine Shimamura, Akiko |
author_facet | Avagyan, Serine Shimamura, Akiko |
author_sort | Avagyan, Serine |
collection | PubMed |
description | Pediatric myelodysplastic syndromes (MDS) often raise concern for an underlying germline predisposition to hematologic malignancies, referred to as germline predisposition herein. With the availability of genetic testing, it is now clear that syndromic features may be lacking in patients with germline predisposition. Many genetic lesions underlying germline predisposition may also be mutated somatically in de novo MDS and leukemias, making it critical to distinguish their germline origin. The verification of a suspected germline predisposition informs therapeutic considerations, guides monitoring pre- and post-treatment, and allows for family counseling. Presentation of MDS due to germline predisposition is not limited to children and spans a wide age range. In fact, the risk of MDS may increase with age in many germline predisposition conditions and can present in adults who lack classical stigmata in their childhood. Furthermore, germline predisposition associated with DDX41 mutations presents with older adult-onset MDS. Although a higher proportion of pediatric patients with MDS will have a germline predisposition, the greater number of MDS diagnoses in adult patients may result in a larger overall number of those with an underlying germline predisposition. In this review, we present a framework for the evaluation of germline predisposition to MDS across all ages. We discuss characteristics of personal and family history, clinical exam and laboratory findings, and integration of genetic sequencing results to assist in the diagnostic evaluation. We address the implications of a diagnosis of germline predisposition for the individual, for their care after MDS therapy, and for family members. Studies on MDS with germline predisposition have provided unique insights into the pathogenesis of hematologic malignancies and mechanisms of somatic genetic rescue vs. disease progression. Increasing recognition in adult patients will inform medical management and may provide potential opportunities for the prevention or interception of malignancy. |
format | Online Article Text |
id | pubmed-8959480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89594802022-03-29 Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies Avagyan, Serine Shimamura, Akiko Front Oncol Oncology Pediatric myelodysplastic syndromes (MDS) often raise concern for an underlying germline predisposition to hematologic malignancies, referred to as germline predisposition herein. With the availability of genetic testing, it is now clear that syndromic features may be lacking in patients with germline predisposition. Many genetic lesions underlying germline predisposition may also be mutated somatically in de novo MDS and leukemias, making it critical to distinguish their germline origin. The verification of a suspected germline predisposition informs therapeutic considerations, guides monitoring pre- and post-treatment, and allows for family counseling. Presentation of MDS due to germline predisposition is not limited to children and spans a wide age range. In fact, the risk of MDS may increase with age in many germline predisposition conditions and can present in adults who lack classical stigmata in their childhood. Furthermore, germline predisposition associated with DDX41 mutations presents with older adult-onset MDS. Although a higher proportion of pediatric patients with MDS will have a germline predisposition, the greater number of MDS diagnoses in adult patients may result in a larger overall number of those with an underlying germline predisposition. In this review, we present a framework for the evaluation of germline predisposition to MDS across all ages. We discuss characteristics of personal and family history, clinical exam and laboratory findings, and integration of genetic sequencing results to assist in the diagnostic evaluation. We address the implications of a diagnosis of germline predisposition for the individual, for their care after MDS therapy, and for family members. Studies on MDS with germline predisposition have provided unique insights into the pathogenesis of hematologic malignancies and mechanisms of somatic genetic rescue vs. disease progression. Increasing recognition in adult patients will inform medical management and may provide potential opportunities for the prevention or interception of malignancy. Frontiers Media S.A. 2022-03-09 /pmc/articles/PMC8959480/ /pubmed/35356204 http://dx.doi.org/10.3389/fonc.2022.813149 Text en Copyright © 2022 Avagyan and Shimamura https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Avagyan, Serine Shimamura, Akiko Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies |
title | Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies |
title_full | Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies |
title_fullStr | Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies |
title_full_unstemmed | Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies |
title_short | Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies |
title_sort | lessons from pediatric mds: approaches to germline predisposition to hematologic malignancies |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959480/ https://www.ncbi.nlm.nih.gov/pubmed/35356204 http://dx.doi.org/10.3389/fonc.2022.813149 |
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