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

Lisa Russell, Melania Capasso, Inga Vater, Takashui Akasaka, Olivier Bernard, Maria Jose Calasanz, Thiruppavaii Chandrasekaran, Elise Chapiro, Stephen Gesk, Mike Griffiths, David Guttery, Claudia Haferlach, Lana Harder, Olaf Heidenreich, Julie Irving, Lyndal Kearney, Florence Nguyen-Khac, Lee Machado, Lynne Minto, Aneela MajidAnthony Moorman, Heather Morrison, Vikki Rand, Jonathan Strefford, Claire Schwab, Holger Tonnies, Martin Dyer, Reiner Siebert, Christine 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 pages10
JournalBlood
Volume114
Issue number13
DOIs
Publication statusPublished - 29 Jul 2009

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Russell, L., Capasso, M., Vater, I., Akasaka, T., Bernard, O., Calasanz, M. J., Chandrasekaran, T., Chapiro, E., Gesk, S., Griffiths, M., Guttery, D., Haferlach, C., Harder, L., Heidenreich, O., Irving, J., Kearney, L., Nguyen-Khac, F., Machado, L., Minto, L., ... Harrison, C. (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