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Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia

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Flex, Elisabetta Petrangeli, Valentina [Istituto Superiore di Sanit à , Rome, 00161, Italy] Stella, Lorenzo [Universit à “ Tor Vergata, ” Rome, 00133, Italy] Chiaretti, Sabina [Universit à “ La Sapienza, ” Rome, 00161, Italy] Hornakova, Tekla [UCL] Knoops, Laurent [UCL] Renauld, Jean-Christophe [UCL] Constantinescu, Stefan N. [UCL] Tartaglia, Marco [Istituto Superiore di Sanit à , Rome, 00161, Italy]

Aberrant signal transduction contributes substantially to leukemogenesis. The Janus kinase 1 (JAK1) gene encodes a cytoplasmic tyrosine kinase that noncovalently associates with a variety of cytokine receptors and plays a nonredundant role in lymphoid cell precursor proliferation, survival, and differentiation. We report that somatic mutations in JAK1 occur in individuals with acute lymphoblastic leukemia ( ALL). JAK1 mutations were more prevalent among adult subjects with the T cell precursor ALL, where they accounted for 18% of cases, and were associated with advanced age at diagnosis, poor response to therapy, and overall prognosis. All mutations were missense, and some were predicted to destabilize interdomain interactions controlling the activity of the kinase. Three mutations that were studied promoted JAK1 gain of function and conferred interleukin (IL)-3- independent growth in Ba/F3 cells and/ or IL-9-independent resistance to dexamethasone-induced apoptosis in T cell lymphoma BW5147 cells. Such effects were associated with variably enhanced activation of multiple downstream signaling pathways. Leukemic cells with mutated JAK1 alleles shared a gene expression signature characterized by transcriptional up-regulation of genes positively controlled by JAK signaling. Our findings implicate dysregulated JAK1 function in ALL, particularly of T cell origin, and point to this kinase as a target for the development of novel antileukemic drugs.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès libre
Publication date 2008
Language Anglais
Journal information "The Journal of Experimental Medicine" - Vol. 205, no. 4, p. 751-8 (2008)
Peer reviewed yes
Publisher Rockefeller Univ Press (New York)
issn 0022-1007
e-issn 1540-9538
Publication status Publié
Affiliations UCL - Cliniques universitaires Saint-Luc
UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
MESH Subject Precursor Cell Lymphoblastic Leukemia-Lymphoma - enzymology - genetics - pathology ; Mutation - genetics ; Mutant Proteins - metabolism ; Molecular Sequence Data ; Models, Molecular ; Mice ; Janus Kinase 1 - genetics ; Humans ; Gene Expression Regulation, Leukemic ; Gene Expression Profiling ; DNA Mutational Analysis ; Cell Line, Tumor ; Base Sequence ; Animals ; Alleles
Links
  1. Armstrong Scott A., Look A. Thomas, Molecular Genetics of Acute Lymphoblastic Leukemia, 10.1200/jco.2005.05.047
  2. Rodig Scott J, Meraz Marco A, White J.Michael, Lampe Pat A, Riley Joan K, Arthur Cora D, King Kathleen L, Sheehan Kathleen C.F, Yin Li, Pennica Diane, Johnson Eugene M, Schreiber Robert D, Disruption of the Jak1 Gene Demonstrates Obligatory and Nonredundant Roles of the Jaks in Cytokine-Induced Biologic Responses, 10.1016/s0092-8674(00)81166-6
  3. Müller Mathias, Briscoe James, Laxton Carl, Guschin Dmitry, Ziemiecki Andrew, Silvennoinen Olli, Harpur Ailsa G., Barbieri Giovanna, Witthuhn Bruce A., Schindler Chris, Pellegrini Sandra, Wilks Andrew F., Ihle James N., Stark George R., Kerr lan M., The protein tyrosine kinase JAK1 complements defects in interferon-α/β and -γ signal transduction, 10.1038/366129a0
  4. Blood., 85, 1300 (1995)
  5. Mol. Cell. Biol., 16, 4710 (1996)
  6. Giordanetto Fabrizio, Kroemer Romano T., Prediction of the structure of human Janus kinase 2 (JAK2) comprising JAK homology domains 1 through 7, 10.1093/protein/15.9.727
  7. Chen M., Cheng A., Candotti F., Zhou Y.-J., Hymel A., Fasth A., Notarangelo L. D., O'Shea J. J., Complex Effects of Naturally Occurring Mutations in the JAK3 Pseudokinase Domain: Evidence for Interactions between the Kinase and Pseudokinase Domains, 10.1128/mcb.20.3.947-956.2000
  8. Lindauer Klaus, Loerting Thomas, Liedl Klaus R., Kroemer Romano T., Prediction of the structure of human Janus kinase 2 (JAK2) comprising the two carboxy-terminal domains reveals a mechanism for autoregulation, 10.1093/protein/14.1.27
  9. Saharinen Pipsa, Silvennoinen Olli, The Pseudokinase Domain Is Required for Suppression of Basal Activity of Jak2 and Jak3 Tyrosine Kinases and for Cytokine-inducible Activation of Signal Transduction, 10.1074/jbc.m205156200
  10. James Chloé, Ugo Valérie, Le Couédic Jean-Pierre, Staerk Judith, Delhommeau François, Lacout Catherine, Garçon Loïc, Raslova Hana, Berger Roland, Bennaceur-Griscelli Annelise, Villeval Jean Luc, Constantinescu Stefan N., Casadevall Nicole, Vainchenker William, A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera, 10.1038/nature03546
  11. Levine Ross L., Wadleigh Martha, Cools Jan, Ebert Benjamin L., Wernig Gerlinde, Huntly Brian J.P., Boggon Titus J., Wlodarska Iwona, Clark Jennifer J., Moore Sandra, Adelsperger Jennifer, Koo Sumin, Lee Jeffrey C., Gabriel Stacey, Mercher Thomas, D’Andrea Alan, Fröhling Stefan, Döhner Konstanze, Marynen Peter, Vandenberghe Peter, Mesa Ruben A., Tefferi Ayalew, Griffin James D., Eck Michael J., Sellers William R., Meyerson Matthew, Golub Todd R., Lee Stephanie J., Gilliland D. Gary, Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis, 10.1016/j.ccr.2005.03.023
  12. Walters Denise K., Mercher Thomas, Gu Ting-Lei, O'Hare Thomas, Tyner Jeffrey W., Loriaux Marc, Goss Valerie L., Lee Kimberly A., Eide Christopher A., Wong Matthew J., Stoffregen Eric P., McGreevey Laura, Nardone Julie, Moore Sandra A., Crispino John, Boggon Titus J., Heinrich Michael C., Deininger Michael W., Polakiewicz Roberto D., Gilliland D. Gary, Druker Brian J., Activating alleles of JAK3 in acute megakaryoblastic leukemia, 10.1016/j.ccr.2006.06.002
  13. Pui Ching-Hon, Evans William E., Treatment of Acute Lymphoblastic Leukemia, 10.1056/nejmra052603
  14. Radtke Simone, Haan Serge, Jörissen Angela, Hermanns Heike M., Diefenbach Sandra, Smyczek Tanya, Schmitz-VandeLeur Hildegard, Heinrich Peter C., Behrmann Iris, Haan Claude, The Jak1 SH2 Domain Does Not Fulfill a Classical SH2 Function in Jak/STAT Signaling but Plays a Structural Role for Receptor Interaction and Up-regulation of Receptor Surface Expression, 10.1074/jbc.m500822200
  15. Haan Claude, Is'harc Hayaatun, Hermanns Heike M., Schmitz-Van de Leur Hildegard, Kerr Ian M., Heinrich Peter C., Grötzinger Joachim, Behrmann Iris, Mapping of a Region within the N Terminus of Jak1 Involved in Cytokine Receptor Interaction, 10.1074/jbc.m106135200
  16. Zhou Yong-Jie, Chen Min, Cusack Nancy A., Kimmel Lida H., Magnuson Kelly S., Boyd James G., Lin Wen, Roberts Joseph L., Lengi Andrea, Buckley Rebecca H., Geahlen Robert L., Candotti Fabio, Gadina Massimo, Changelian Paul S., O'Shea John J., Unexpected Effects of FERM Domain Mutations on Catalytic Activity of Jak3, 10.1016/s1097-2765(01)00398-7
  17. Levine R. L., The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia, 10.1182/blood-2005-05-1898
  18. Gokbuget N., Hoelzer D., Treatment of Adult Acute Lymphoblastic Leukemia, 10.1182/asheducation-2006.1.133
  19. Baldus Claudia D., Burmeister Thomas, Martus Peter, Schwartz Stefan, Gökbuget Nicola, Bloomfield Clara D., Hoelzer Dieter, Thiel Eckhard, Hofmann Wolf K., High Expression of the ETS Transcription FactorERGPredicts Adverse Outcome in Acute T-Lymphoblastic Leukemia in Adults, 10.1200/jco.2006.06.1580
  20. Ferrando Adolfo A, Neuberg Donna S, Dodge Richard K, Paietta Elisabeth, Larson Richard A, Wiernik Peter H, Rowe Jacob M, Caligiuri Michael A, Bloomfield Clara D, Look A Thomas, Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia, 10.1016/s0140-6736(04)15542-6
  21. Zhu Y.-M., NOTCH1 Mutations in T-Cell Acute Lymphoblastic Leukemia: Prognostic Significance and Implication in Multifactorial Leukemogenesis, 10.1158/1078-0432.ccr-05-2832
  22. Yeoh Eng-Juh, Ross Mary E, Shurtleff Sheila A, Williams W.Kent, Patel Divyen, Mahfouz Rami, Behm Fred G, Raimondi Susana C, Relling Mary V, Patel Anami, Cheng Cheng, Campana Dario, Wilkins Dawn, Zhou Xiaodong, Li Jinyan, Liu Huiqing, Pui Ching-Hon, Evans William E, Naeve Clayton, Wong Limsoon, Downing James R, Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling, 10.1016/s1535-6108(02)00032-6
  23. Vitale Antonella, Guarini Anna, Chiaretti Sabina, Foà Robin, The changing scene of adult acute lymphoblastic leukemia : , 10.1097/01.cco.0000245317.82391.1b
  24. Chiaretti S., Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to therapy and survival, 10.1182/blood-2003-09-3243
  25. Thomas Xavier, Emerging drugs for adult acute lymphoblastic leukaemia, 10.1517/14728214.10.3.591
  26. Yamaoka Kunihiro, Saharinen Pipsa, Pesu Marko, Holt Vance ET, Silvennoinen Olli, O'Shea John J, 10.1186/gb-2004-5-12-253
  27. Schindler Christian, Levy David E., Decker Thomas, JAK-STAT Signaling: From Interferons to Cytokines, 10.1074/jbc.r700016200
  28. Murray P. J., The JAK-STAT Signaling Pathway: Input and Output Integration, 10.4049/jimmunol.178.5.2623
Bibliographic reference Flex, Elisabetta ; Petrangeli, Valentina ; Stella, Lorenzo ; Chiaretti, Sabina ; Hornakova, Tekla ; et. al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. In: The Journal of Experimental Medicine, Vol. 205, no. 4, p. 751-8 (2008)
Permanent URL http://hdl.handle.net/2078.1/36654