Journal ArticleDOI
MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort.
Philip A. Beer,Peter J. Campbell,Linda M. Scott,Anthony J. Bench,Wendy N. Erber,David Bareford,Bridget S. Wilkins,John T. Reilly,Hans Carl Hasselbalch,Richard Bowman,Keith Wheatley,Georgina Buck,Claire N. Harrison,Anthony R. Green +13 more
TLDR
It is demonstrated that MPL mutations outside exon 10 are uncommon in platelet cDNA and 4 different exon10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF are identified.About:
This article is published in Blood.The article was published on 2008-07-01. It has received 386 citations till now. The article focuses on the topics: Essential thrombocythemia & Polycythemia vera.read more
Citations
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Journal ArticleDOI
Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2 , MPL , TET2 , ASXL1 , CBL , IDH and IKZF1
TL;DR: The functional consequences of MPN-associated mutations including unregulated JAK-STAT signaling, epigenetic modulation of transcription and abnormal accumulation of oncoproteins are not clear as to whether and how these abnormalities contribute to disease initiation, clonal evolution or blastic transformation.
Journal ArticleDOI
JAK/STAT signaling in hematological malignancies
William Vainchenker,William Vainchenker,William Vainchenker,Stefan N. Constantinescu,Stefan N. Constantinescu +4 more
TL;DR: The nature and respective contribution of mutations dysregulating the JAK/STAT pathway in hematological malignancies are discussed and examples in which such mutations drive the disease, contribute to the phenotype, or provide a survival and proliferative advantage are presented.
Journal ArticleDOI
Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms
TL;DR: The genetic landscape of classical myeloproliferative neoplasm (MPN) is in large part elucidated and factors other than somatic mutations play an important role in disease initiation as well as disease progression such as germ line predisposition, inflammation, and aging.
Journal ArticleDOI
New mutations and pathogenesis of myeloproliferative neoplasms.
William Vainchenker,William Vainchenker,François Delhommeau,François Delhommeau,Stefan N. Constantinescu,Stefan N. Constantinescu,Olivier Bernard,Olivier Bernard,Olivier Bernard +8 more
TL;DR: Loss-of-function mutations in 3 genes involved in epigenetic regulation, TET2, ASXL1, and EZH2, may be early events preceding JAK2V617F but may also occur late during disease progression, and IZF1 deletions or TP53 mutations are mainly found at transformation phases and are present at greater frequency in de novo acute myeloid leukemias.
Journal ArticleDOI
Myeloproliferative Neoplasms: Molecular Pathophysiology, Essential Clinical Understanding, and Treatment Strategies
TL;DR: Oncologists on pathogenesis, contemporary diagnosis, risk stratification, and treatment strategies in BCR-ABL1-negative myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).
References
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Journal ArticleDOI
A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
Robert Kralovics,Francesco Passamonti,Andreas Buser,Soon Siong Teo,Ralph Tiedt,Jakob Passweg,André Tichelli,Mario Cazzola,Radek C. Skoda +8 more
TL;DR: Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.
Journal ArticleDOI
Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.
E. Joanna Baxter,Linda M. Scott,Peter J. Campbell,Clare L. East,Nasios Fourouclas,Soheila Swanton,George S. Vassiliou,Anthony J. Bench,Elaine M. Boyd,Natasha Curtin,Michael A. Scott,Wendy N. Erber,Anthony R. Green,Anthony R. Green +13 more
TL;DR: A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder and its presence in all erythropoietin-independent erythroid colonies demonstrates a link with growth factor hypersensitivity, a key biological feature of these disorders.
Journal ArticleDOI
A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
Chloé James,Valérie Ugo,Jean-Pierre Le Couedic,Judith Staerk,François Delhommeau,Catherine Lacout,Loïc Garçon,Hana Raslova,Roland Berger,Annelise Bennaceur-Griscelli,Jean-Luc Villeval,Stefan N. Constantinescu,Nicole Casadevall,William Vainchenker +13 more
TL;DR: A clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (> 80%) polycythaemia vera patients leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity and induces erythrocytosis in a mouse model.
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
MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.
Yana Pikman,Benjamin H. Lee,Thomas Mercher,Elizabeth McDowell,Benjamin L. Ebert,Benjamin L. Ebert,Maricel Gozo,Adam Cuker,Gerlinde Wernig,Sandra A. Moore,Ilene Galinsky,Daniel J. DeAngelo,Jennifer J. Clark,Stephanie J. Lee,Todd R. Golub,Todd R. Golub,Todd R. Golub,Martha Wadleigh,D. Gary Gilliland,D. Gary Gilliland,D. Gary Gilliland,Ross L. Levine,Ross L. Levine +22 more
TL;DR: The JAK2V617F allele has been identified in patients with polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis with myeloid metaplasia (MF).
Related Papers (5)
MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.
Yana Pikman,Benjamin H. Lee,Thomas Mercher,Elizabeth McDowell,Benjamin L. Ebert,Benjamin L. Ebert,Maricel Gozo,Adam Cuker,Gerlinde Wernig,Sandra A. Moore,Ilene Galinsky,Daniel J. DeAngelo,Jennifer J. Clark,Stephanie J. Lee,Todd R. Golub,Todd R. Golub,Todd R. Golub,Martha Wadleigh,D. Gary Gilliland,D. Gary Gilliland,D. Gary Gilliland,Ross L. Levine,Ross L. Levine +22 more