Dysfunctional telomeres and hematological disorders.
Differentiation
; 100: 1-11, 2018.
Article
em En
| MEDLINE
| ID: mdl-29331736
ABSTRACT
Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic stem and progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and differentiation. We also discuss how both the increased risk of myelodysplastic syndromes and other hematological malignancies that is associated with telomere disorders and the discovery of cancer-associated somatic mutations in the shelterin components challenge the conventional interpretation that telomere defects are cancer-protective rather than cancer-promoting.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças da Medula Óssea
/
Encurtamento do Telômero
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article