Br J Haematol. 2007 May;137(4):337-41.

Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome.

De Vita S, Mulligan C, McElwaine S, Dagna-Bricarelli F, Spinelli M, Basso G, Nizetic D, Groet J.

Source

Centre for Haematology, Institute of Cell and Molecular Science, Barts & The London, Queen Mary's School of Medicine, University of London, London, UK.

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.

PMID:: 17456055; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

Research Support, Non-U.S. Gov't

MeSH Terms

Substances

Grant Support

C.51/Telethon/Italy

LinkOut - more resources

Full Text Sources

Medical

Supplemental Content

Save items

Related citations in PubMed

Functional analysis of JAK3 mutations in transient myeloproliferative disorder and acute megakaryoblastic leukaemia accompanying Down syndrome. [Br J Haematol. 2008]
Functional analysis of JAK3 mutations in transient myeloproliferative disorder and acute megakaryoblastic leukaemia accompanying Down syndrome.
Sato T, Toki T, Kanezaki R, Xu G, Terui K, Kanegane H, Miura M, Adachi S, Migita M, Morinaga S, et al. Br J Haematol. 2008 May; 141(5):681-8. Epub 2008 Apr 7.
Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome. [Blood. 2003]
Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome.
Xu G, Nagano M, Kanezaki R, Toki T, Hayashi Y, Taketani T, Taki T, Mitui T, Koike K, Kato K, et al. Blood. 2003 Oct 15; 102(8):2960-8. Epub 2003 Jun 19.
Natural history of GATA1 mutations in Down syndrome. [Blood. 2004]
Natural history of GATA1 mutations in Down syndrome.
Ahmed M, Sternberg A, Hall G, Thomas A, Smith O, O'Marcaigh A, Wynn R, Stevens R, Addison M, King D, et al. Blood. 2004 Apr 1; 103(7):2480-9. Epub 2003 Dec 4.
Review Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis. [Br J Haematol. 2009]
Review Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis.
Roy A, Roberts I, Norton A, Vyas P. Br J Haematol. 2009 Oct; 147(1):3-12. Epub 2009 Jul 6.
Review Down myeloid disorders: a paradigm for childhood preleukaemia and leukaemia and insights into normal megakaryopoiesis. [Early Hum Dev. 2006]
Review Down myeloid disorders: a paradigm for childhood preleukaemia and leukaemia and insights into normal megakaryopoiesis.
Vyas P, Roberts I. Early Hum Dev. 2006 Dec; 82(12):767-73. Epub 2006 Oct 24.

See reviews... See all...

Cited by 7 PubMed Central articles

Advances in the Biology of Acute Lymphoblastic Leukemia-From Genomics to the Clinic. [J Adolesc Young Adult Oncol. 2...]
Advances in the Biology of Acute Lymphoblastic Leukemia-From Genomics to the Clinic.
Mullighan CG, Willman CL. J Adolesc Young Adult Oncol. 2011 Jun; 1(2):77-86.
Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21. [J Biomed Res. 2010]
Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21.
Ruparelia A, Wiseman F, Sheppard O, Tybulewicz VL, Fisher EM. J Biomed Res. 2010 Mar; 24(2):87-99.
Review JAK3: a two-faced player in hematological disorders. [Int J Biochem Cell Biol. 2009]
Review JAK3: a two-faced player in hematological disorders.
Cornejo MG, Boggon TJ, Mercher T. Int J Biochem Cell Biol. 2009 Dec; 41(12):2376-9. Epub 2009 Sep 9.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
ClinVar
Clinical variations associated with publication
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Gene (GeneRIF)
Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
MedGen
Related information in MedGen
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
SNP (Cited)
Nucleotide polymorphism records from dbSNP that have NCBI dbSNP identifiers reported in the PubMed abstract of the current articles.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
SNP
Nucleotide polymorphism records from dbSNP that have current articles as submitter-provided references.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome.
Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome.
Br J Haematol. 2007 May ;137(4):337-41.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: