Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia.

Lisa J Russell, Melania Capasso, Inga Vater, Takashi Akasaka, Olivier A Bernard, Maria J Calasanz, Thiruppavaii Chandrasekaran, Elise Chapiro, Stephan Gesk, Mike Griffiths, David S Guttery, Claudia Haferlach, Lana Harder, Olaf Heidenreich, Julie Irving, Lyndal Kearney, Florence Nguyen-Khac, Lee Machado, Lynne Minto, Aneela MajidAnthony V Moorman, Heather Morrison, Vikki Rand, Jonathon C Strefford, Claire Schwab, Holger Tonnies, Martin J S Dyer, Reiner Siebert, Christine J Harrison

    Research output: Contribution to journalArticle

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)2688-2698
    Number of pages11
    JournalBlood
    Volume114
    Issue number13
    DOIs
    Publication statusPublished - 31 Jul 2009

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  • Cite this

    Russell, L. J., Capasso, M., Vater, I., Akasaka, T., Bernard, O. A., Calasanz, M. J., Chandrasekaran, T., Chapiro, E., Gesk, S., Griffiths, M., Guttery, D. S., Haferlach, C., Harder, L., Heidenreich, O., Irving, J., Kearney, L., Nguyen-Khac, F., Machado, L., Minto, L., ... Harrison, C. J. (2009). Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood, 114(13), 2688-2698. https://doi.org/10.1182/blood-2009-03-208397