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 journalArticlepeer-review

    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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