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Blood, 24 September 2009, Vol. 114, No. 13, pp. 2688-2698. Prepublished online as a Blood First Edition Paper on July 29, 2009; DOI 10.1182/blood-2009-03-208397. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2009-03-208397v1 114/13/2688    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Russell, L. J. Articles by Harrison, C. J. PubMed PubMed Citation Articles by Russell, L. J. Articles by Harrison, C. J. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia Lisa J. Russell1,*, Melania Capasso2,*, Inga Vater3,*, Takashi Akasaka2, Olivier A. Bernard4, Maria Jose Calasanz5, Thiruppavaii Chandrasekaran2, Elise Chapiro4, Stephan Gesk3, Mike Griffiths6, David S. Guttery2, Claudia Haferlach7, Lana Harder3, Olaf Heidenreich8, Julie Irving8, Lyndal Kearney9, Florence Nguyen-Khac4, Lee Machado2, Lynne Minto8, Aneela Majid2, Anthony V. Moorman1, Heather Morrison1, Vikki Rand1, Jonathan C. Strefford10, Claire Schwab1, Holger Tönnies3, Martin J. S. Dyer2,, Reiner Siebert3,, and Christine J. Harrison1, 1 Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; 2 Medical Research Council Toxicology Unit, Leicester University, Leicester, United Kingdom; 3 Institute of Human Genetics, Christian Albrechts University, and University Hospital Schleswig-Holstein, Kiel, Germany; 4 Inserm E210, Hôpital Necker Enfants Malade, Paris, France; 5 Department of Genetics, University of Navarra, Pamplona, Spain; 6 West Midlands Regional Genetics Laboratory, Birmingham Women's Hospital, Birmingham, United Kingdom; 7 MLL Münchner Leukämielabor GmbH, Munich, Germany; 8 Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom; 9 Section of Haemato-Oncology, Institute of Cancer Research, Surrey, United Kingdom; and 10 Cancer Genomics Group, Cancer Sciences Division, University of Southampton, Southampton, United Kingdom We report 2 novel, cryptic chromosomal abnormalities in precursor B-cell acute lymphoblastic leukemia (BCP-ALL): a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32), in 33 patients and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32), in 64 patients, involving the pseudoautosomal region (PAR1) of the sex chromosomes. The incidence of these abnormalities was 5% in childhood ALL (0.8% with the translocation, 4.2% with the deletion). Patients with the translocation were older (median age, 16 years), whereas the patients with the deletion were younger (median age, 4 years). The 2 abnormalities result in deregulated expression of the cytokine receptor, cytokine receptor-like factor 2, CRLF2 (also known as thymic stromal-derived lymphopoietin receptor, TSLPR). Overexpression of CRLF2 was associated with activation of the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation and indicating a causal role of CRLF2 overexpression in lymphoid transformation. In Down syndrome (DS) ALL and 2 non-DS BCP-ALL cell lines, CRLF2 deregulation was associated with mutations of the JAK2 pseudokinase domain, suggesting oncogenic cooperation as well as highlighting a link between non-DS ALL and JAK2 mutations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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