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- Title
Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome.
- Authors
De Vita, Serena; Mulligan, Claire; McElwaine, Suzanne; Dagna-Bricarelli, Franca; Spinelli, Monica; Basso, Giuseppe; Nizetic, Dean; Groet, Jürgen
- 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.
- Publication
British journal of haematology, 2007, Vol 137, Issue 4, p337
- ISSN
0007-1048
- Publication type
Journal Article
- DOI
10.1111/j.1365-2141.2007.06574.x