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Aberrant signal transduction pathways in myeloproliferative neoplasms.

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Kota, J Caceres, Nancy [UCL] Constantinescu, Stefan N. [UCL]

The BCR-ABL-negative myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), entered the spotlight in 2005 when the unique somatic acquired JAK2 V617F mutation was described in >95% of PV and in 50% of ET and PMF patients. For the very rare PV patients who do not harbor the JAK2 V617F mutation, exon 12 JAK2 mutants were discovered also to result in activated forms of JAK2. A minority of ET and PMF patients harbor mutations that constitutively activate the thrombopoietin receptor (TpoR). In bone marrow reconstitution models based on retroviral transduction, the phenotype induced by JAK2 V617F is less severe and different from the rapid fatal myelofibrosis induced by TpoR W515L. The reasons for these differences are unknown. Exactly by which mechanism(s) one acquired somatic mutation, JAK2 V617F, can promote three different diseases remains a mystery, although gene dosage and host genetic variation might have important functions. We review the recent progress made in deciphering signaling anomalies in PV, ET and PMF, with an emphasis on the relationship between JAK2 V617F and cytokine receptor signaling and on cross-talk with several other signaling pathways.Leukemia advance online publication, 4 September 2008; doi:10.1038/leu.2008.236.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't, Review
Access type Accès restreint
Publication date 2008
Journal information "Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K" - Vol. 22, no. 10, p. 1828-40 (2008)
Peer reviewed yes
issn 0887-6924
e-issn 1476-5551
Publication status Publié
Affiliation UCL
MESH Subject Tumor Necrosis Factor-alpha - physiology ; Transforming Growth Factor beta - physiology ; Thrombocythemia, Essential - genetics - physiopathology ; Suppressor of Cytokine Signaling Proteins - physiology ; Signal Transduction ; STAT Transcription Factors - physiology ; Receptors, Thrombopoietin - physiology ; Receptors, Granulocyte Colony-Stimulating Factor - physiology ; Receptors, Erythropoietin - physiology ; Primary Myelofibrosis - genetics - physiopathology ; Polycythemia Vera - genetics - physiopathology ; Phosphorylation ; Mutation ; Janus Kinase 2 - antagonists & inhibitors - genetics - physiology ; Humans ; Hematopoietic Stem Cells - physiology ; Disease Models, Animal ; Animals
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Bibliographic reference Kota, J ; Caceres, Nancy ; Constantinescu, Stefan N.. Aberrant signal transduction pathways in myeloproliferative neoplasms.. In: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K, Vol. 22, no. 10, p. 1828-40 (2008)
Permanent URL http://hdl.handle.net/2078.1/14187