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 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 MajidAnthony V. Moorman, Heather Morrison, Vikki Rand, Jonathan C. Strefford, Claire Schwab, Holger Tönnies, 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 (US)
Pages (from-to)2688-2698
Number of pages11
JournalBlood
Volume114
Issue number13
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia'. Together they form a unique fingerprint.

  • 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