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 |
| DOI: | https://doi.org/10.1182/blood-2009-03-208397 |
| ISSN: | 0006-4971 |
| Status: | Published / Disseminated |
| URI: | http://nectar.northampton.ac.uk/id/eprint/5686 |
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