Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome.
Br J Haematol
; 137(4): 337-41, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17456055
ABSTRACT
Acquired mutations activating Janus kinase 3 (jak3) have been reported in Down syndrome (DS) and non-DS patients with acute megakaryoblastic leukaemia (AMKL). This highlighted jak3-activation as an important event in the pathogenesis of AMKL, and predicted inhibitors of jak3 as conceptual therapeutics for AMKL. Of 16 DS-transient myeloproliferative disorder (TMD)/AMKL patients tested, seven showed JAK3 mutations. Three mutations deleted the kinase (JH1) domain, abolishing the main function of jak3. Another patient displayed a mutation identical to a previously reported inherited loss-of-function causing severe combined immunodeficiency. Our data suggest that both gain-, and loss-of function mutations of jak3 can be acquired in DS-TMD/AMKL.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Megacarioblástica Aguda
/
Síndrome de Down
/
Janus Quinase 3
/
Mutação
Limite:
Humans
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2007
Tipo de documento:
Article