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

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

  • Blood. 2009 Sep 24;114(13):2688-98. doi: 10.1182/blood-2009-03-208397.
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
Affiliations

Affiliation

  • 1 Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom.
PMID: 19641190 DOI: 10.1182/blood-2009-03-208397
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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