Journal ArticleDOI
Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia
Marco Tartaglia,Charlotte M. Niemeyer,Alessandra Fragale,Alessandra Fragale,Xiaoling Song,Jochen Buechner,Andreas Jung,Karel Hählen,Henrik Hasle,Jonathan D. Licht,Bruce D. Gelb +10 more
TLDR
It is reported that individuals with Noonan syndrome and juvenile myelomonocytic leukemia have germline mutations in PTPN11 and that somatic mutations in MDS and AML account for 34% of non-syndromic JMML.Abstract:
We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML. Furthermore, we found mutations in PTPN11 in a small percentage of individuals with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML). Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.read more
Citations
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The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes
James W. Vardiman,Juergen Thiele,Daniel A. Arber,Richard D. Brunning,Michael J. Borowitz,Anna Porwit,Nancy L. Harris,Michelle M. Le Beau,Eva Hellström-Lindberg,Ayalew Tefferi,Clara D. Bloomfield +10 more
TL;DR: The classification of myeloid neoplasms and acute leukemia is highlighted with the aim of familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes.
Journal ArticleDOI
Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.
Ross L. Levine,Ross L. Levine,Martha Wadleigh,Jan Cools,Benjamin L. Ebert,Benjamin L. Ebert,Gerlinde Wernig,Brian J. P. Huntly,Titus J. Boggon,Iwona Wlodarska,Jennifer J. Clark,Sandra A. Moore,Jennifer Adelsperger,Sumin Koo,Jeffrey C. Lee,Stacey Gabriel,Thomas Mercher,Alan D. D'Andrea,Stefan Fröhling,Konstanze Döhner,Peter Marynen,Peter Vandenberghe,Ruben A. Mesa,Ayalew Tefferi,James D. Griffin,Michael J. Eck,William R. Sellers,William R. Sellers,Matthew Meyerson,Matthew Meyerson,Todd R. Golub,Todd R. Golub,Todd R. Golub,Stephanie J. Lee,D. Gary Gilliland,D. Gary Gilliland,D. Gary Gilliland +36 more
TL;DR: High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations.
Journal ArticleDOI
Targeting the IL-6/JAK/STAT3 signalling axis in cancer.
TL;DR: Treatments that target the IL-6/JAK/STAT3 pathway in patients with cancer are poised to provide therapeutic benefit by directly inhibiting tumour cell growth and by stimulating antitumour immunity.
Journal ArticleDOI
Protein tyrosine phosphatases: from genes, to function, to disease
TL;DR: Recent breakthroughs in understanding of the role of the PTPs in the regulation of signal transduction and the aetiology of human disease are described.
Journal ArticleDOI
Hyperactive Ras in developmental disorders and cancer.
TL;DR: The implications of germline mutations in the Ras–Raf–MEK–ERK pathway for understanding normal developmental processes and cancer pathogenesis are discussed.
References
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Journal ArticleDOI
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome.
Marco Tartaglia,Marco Tartaglia,Ernest L. Mehler,Rosalie Goldberg,Giuseppe Zampino,Han G. Brunner,Hannie Kremer,Ineke van der Burgt,Andrew H. Crosby,Andra Ion,Steve Jeffery,Kamini Kalidas,Michael A. Patton,Raju Kucherlapati,Bruce D. Gelb +14 more
TL;DR: It is shown that missense mutations in PTPN11—a gene encoding the nonreceptor protein tyrosine phosphatase SHP-2, which contains two Src homology 2 (SH2) domains—cause Noonan syndrome and account for more than 50% of the cases that were examined.
Journal ArticleDOI
Crystal Structure of the Tyrosine Phosphatase SHP-2
TL;DR: The structure of the SHP-2 tyrosine phosphatase, determined at 2.0 angstroms resolution, shows how its catalytic activity is regulated by its two SH2 domains.
Journal ArticleDOI
PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity
Marco Tartaglia,Marco Tartaglia,Kamini Kalidas,Adam Shaw,Xiaoling Song,Dan L. Musat,Ineke van der Burgt,Han G. Brunner,Débora Romeo Bertola,Andrew H. Crosby,Andra Ion,Raju Kucherlapati,Steve Jeffery,Michael A. Patton,Bruce D. Gelb +14 more
TL;DR: The spectrum and distribution of PTPN11 mutations in a large, well-characterized cohort with NS revealed that pulmonic stenosis was more prevalent among the group of subjects with NS who had PTP N11 mutations than it was in the group without them, andotype-phenotype analysis revealed that hypertrophic cardiomyopathy was less prevalent among those with PTPn11 mutations.
Journal ArticleDOI
Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells
Gideon Bollag,D. W. Clapp,S. Shih,Felix Adler,You Yan Zhang,Pamela J. Thompson,Beverly J. Lange,M. H. Freedman,F. Mccormick,Tyler Jacks,Kevin Shannon +10 more
TL;DR: It is shown that primary leukaemic cells from children with NF1 show a selective decrease in NF1-like GTPase activating protein (GAP) activity for Ras but retain normal cellular GAP activity.
Journal ArticleDOI
Hypertelorism With Turner Phenotype: A New Syndrome With Associated Congenital Heart Disease
TL;DR: Nine patients with remarkably similar facies with a previously unrecognized syndrome of valvular pulmonary stenosis and multiple extra cardiac anomalies with similar associated lesions are reported on in 1962.
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