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.

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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:

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:

Language:

English

DOI:

10.1182/blood-2009-03-208397

ISSN:

0006-4971

Status:

Published / Disseminated