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. 2009 Sep 24;114(13):2688-98.
doi: 10.1182/blood-2009-03-208397. Epub 2009 Jul 29.

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

Lisa J Russell  1 , Melania Capasso, Inga Vater, Takashi Akasaka, Olivier A Bernard, Maria Jose 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 Majid, Anthony V Moorman, Heather Morrison, Vikki Rand, Jonathan C Strefford, Claire Schwab, Holger Tönnies, Martin J S Dyer, Reiner Siebert, Christine J Harrison
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Free article

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

Lisa J Russell et al. Blood. .
Free article

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.

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