Pathogenesis of myeloproliferative neoplasms

被引:93
作者
Skoda, Radek C. [1 ]
Duek, Adrian [2 ]
Grisouard, Jean [1 ]
机构
[1] Univ Basel Hosp, Dept Biomed, Expt Hematol, CH-4031 Basel, Switzerland
[2] Chaim Sheba Med Ctr, Hematol Inst, Ramat Gan, Israel
关键词
JAK-STAT PATHWAY; HEMATOPOIETIC-CELLS LEADS; PSEUDOKINASE DOMAIN; POLYCYTHEMIA-VERA; STEM-CELL; THROMBOPOIETIN RECEPTOR; DOWN-SYNDROME; MOUSE MODEL; ESSENTIAL THROMBOCYTHEMIA; TYROSINE PHOSPHORYLATION;
D O I
10.1016/j.exphem.2015.06.007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Major progress has been recently made in understanding the molecular pathogenesis of myeloproliferative neoplasms (MPN). Mutations in one of four genes-JAK2, MPL, CALR, and CSF3R-can be found in the vast majority of patients with MPN and represent driver mutations that can induce the MPN phenotype. Hyperactive JAK/STAT signaling appears to be the common denominator of MPN, even in patients with CALR mutations and the so-called "triple-negative" MPN, where the driver gene mutation is still unknown. Mutations in epigenetic regulators, transcription factors, and signaling components modify the course of the disease and can contribute to disease initiation and/or progression. The central role of JAK2 in MPN allowed development of small molecular inhibitors that are in clinical use and are active in almost all patients with MPN. Advances in understanding the mechanism of JAK2 activation open new perspectives of developing the next generation of inhibitors that will be selective for the mutated forms of JAK2. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.
引用
收藏
页码:599 / 608
页数:10
相关论文
共 133 条
[1]   POLYCYTHEMIA-VERA - STEM-CELL AND PROBABLE CLONAL ORIGIN OF DISEASE [J].
ADAMSON, JW ;
FIALKOW, PJ ;
MURPHY, S ;
PRCHAL, JF ;
STEINMANN, L .
NEW ENGLAND JOURNAL OF MEDICINE, 1976, 295 (17) :913-916
[2]   Critical Role of Jak2 in the Maintenance and Function of Adult Hematopoietic Stem Cells [J].
Akada, Hajime ;
Akada, Saeko ;
Hutchison, Robert E. ;
Sakamoto, Kazuhito ;
Wagner, Kay-Uwe ;
Mohi, Golam .
STEM CELLS, 2014, 32 (07) :1878-1889
[3]   Essential role of STAT3 in the control of the acute-phase response as revealed by inducible gene activation in the liver [J].
Alonzi, T ;
Maritano, D ;
Gorgoni, B ;
Rizzuto, G ;
Libert, C ;
Poli, V .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (05) :1621-1632
[4]   Modulation of Activation-Loop Phosphorylation by JAK Inhibitors Is Binding Mode Dependent [J].
Andraos, Rita ;
Qian, Zhiyan ;
Bonenfant, Debora ;
Rubert, Joelle ;
Vangrevelinghe, Eric ;
Scheufler, Clemens ;
Marque, Fanny ;
Regnier, Catherine H. ;
De Pover, Alain ;
Ryckelynck, Hugues ;
Bhagwat, Neha ;
Koppikar, Priya ;
Goel, Aviva ;
Wyder, Lorenza ;
Tavares, Gisele ;
Baffert, Fabienne ;
Pissot-Soldermann, Carole ;
Manley, Paul W. ;
Gaul, Christoph ;
Voshol, Hans ;
Levine, Ross L. ;
Sellers, William R. ;
Hofmann, Francesco ;
Radimerski, Thomas .
CANCER DISCOVERY, 2012, 2 (06) :512-523
[5]   Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms [J].
Arranz, Lorena ;
Sanchez-Aguilera, Abel ;
Martin-Perez, Daniel ;
Isern, Joan ;
Langa, Xavier ;
Tzankov, Alexandar ;
Lundberg, Pontus ;
Muntion, Sandra ;
Tzeng, Yi-Shiuan ;
Lai, Dar-Ming ;
Schwaller, Juerg ;
Skoda, Radek C. ;
Mendez-Ferrer, Simon .
NATURE, 2014, 512 (7512) :78-+
[6]   The molecular regulation of Janus kinase (JAK) activation [J].
Babon, Jeffrey J. ;
Lucet, Isabelle S. ;
Murphy, James M. ;
Nicola, Nicos A. ;
Varghese, Leila N. .
BIOCHEMICAL JOURNAL, 2014, 462 :1-13
[7]   Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F [J].
Bandaranayake, Rajintha M. ;
Ungureanu, Daniela ;
Shan, Yibing ;
Shaw, David E. ;
Silvennoinen, Olli ;
Hubbard, Stevan R. .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2012, 19 (08) :754-759
[8]   Co-targeting the PI3K/mTOR and JAK2 signalling pathways produces synergistic activity against myeloproliferative neoplasms [J].
Bartalucci, Niccolo ;
Tozzi, Lorenzo ;
Bogani, Costanza ;
Martinelli, Serena ;
Rotunno, Giada ;
Villeval, Jean-Luc ;
Vannucchi, Alessandro M. .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2013, 17 (11) :1385-1396
[9]  
Bartalucci Niccolo, 2013, Clin Lymphoma Myeloma Leuk, V13 Suppl 2, pS307, DOI 10.1016/j.clml.2013.07.011
[10]   Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders [J].
Baxter, EJ ;
Scott, LM ;
Campbell, PJ ;
East, C ;
Fourouclas, N ;
Swanton, S ;
Vassiliou, GS ;
Bench, AJ ;
Boyd, EM ;
Curtin, N ;
Scott, MA ;
Erber, WN ;
Green, AR .
LANCET, 2005, 365 (9464) :1054-1061