Northampton Electronic Collection of Theses and Research

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

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., Majid, A., Moorman, A., Morrison, H., Rand, V., Strefford, J., Schwab, C., Tonnies, H., Dyer, M., Siebert, R. and 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), pp. 2688-2698. 0006-4971.

Item Type: 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
Subjects: R Medicine > RC Internal medicine > RC633 Diseases of the blood and blood-forming organs
R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology
Creators: Russell, Lisa, Capasso, Melania, Vater, Inga, Akasaka, Takashui, Bernard, Olivier, Calasanz, Maria Jose, Chandrasekaran, Thiruppavaii, Chapiro, Elise, Gesk, Stephen, Griffiths, Mike, Guttery, David, Haferlach, Claudia, Harder, Lana, Heidenreich, Olaf, Irving, Julie, Kearney, Lyndal, Nguyen-Khac, Florence, Machado, Lee, Minto, Lynne, Majid, Aneela, Moorman, Anthony, Morrison, Heather, Rand, Vikki, Strefford, Jonathan, Schwab, Claire, Tonnies, Holger, Dyer, Martin, Siebert, Reiner and Harrison, Christine
Publisher: American Society of Hematology
Northamptonshire and East Midlands: Health
Faculties, Divisions and Institutes: University Faculties, Divisions and Research Centres - OLD > Faculty of Health & Society
University Faculties, Divisions and Research Centres - OLD > Research Centre > Institute of Health and Wellbeing > Ageing Research Centre
Research Centres > Centre for Health Sciences and Services
Research Centres > Centre for Physical Activity and Life Sciences
Date: 24 September 2009
Date Type: Submission
Page Range: pp. 2688-2698
Journal or Publication Title: Blood
Volume: 114
Number: 13
Language: English
ISSN: 0006-4971
Status: Published / Disseminated

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