Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in thrombopoietin.
Blood
; 130(7): 875-880, 2017 08 17.
Article
em En
| MEDLINE
| ID: mdl-28559357
ABSTRACT
We report 5 individuals in 3 unrelated families with severe thrombocytopenia progressing to trilineage bone marrow failure (BMF). Four of the children received hematopoietic stem cell transplants and all showed poor graft function with persistent severe cytopenias even after repeated transplants with different donors. Exome and targeted sequencing identified mutations in the gene encoding thrombopoietin (THPO) THPO R99W, homozygous in affected children in 2 families, and THPO R157X, homozygous in the affected child in the third family. Both mutations result in a lack of THPO in the patients' serum. For the 2 surviving patients, improvement in trilineage hematopoiesis was achieved following treatment with a THPO receptor agonist. These studies demonstrate that biallelic loss-of-function mutations in THPO cause BMF, which is unresponsive to transplant due to a hematopoietic cell-extrinsic mechanism. These studies provide further support for the critical role of the MPL-THPO pathway in hematopoiesis and highlight the importance of accurate genetic diagnosis to inform treatment decisions for BMF.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombopoetina
/
Medula Óssea
/
Transplante de Medula Óssea
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Child
/
Child, preschool
/
Female
/
Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article