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

L Russell, M Capasso, I Vater, T Akasaka, OA Bernard, MJ Calasanz, T Chandrasekaran, E Chapiro, S Gesk, Michael Griffiths, DS Guttery, C Haferlach, L Harder, O Heidenreich, J Irving, L Kearney, F Nguyen-Khac, L Machado, L Minto, A MajidAV Moorman, H Morrison, V Rand, JC Strefford, C Schwab, H Tonnies, MJS Dyer, R Siebert, CJ Harrison

Research output: Contribution to journalArticle

339 Citations (Scopus)

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 - 24 Sep 2009

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