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
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.
2688-2698
Russell, Lisa J.
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Capasso, Melania
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Vater, Inga
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Bernard, Olivier A.
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Chandrasekaran, Thiruppavaii
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Griffith, Mike
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Irving, Julie
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Kearney, Lyndal
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Moorman, Anthony V.
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Rand, Vikki
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Strefford, Jonathan C.
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Dyer, Martin J. S.
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Siebert, Reiner
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Harrison, Christine J.
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Takashi, Akasaka
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Calasanz, Maria Jose
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Chapiro, Elise
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Gesk, Stephan
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Guttery, David S.
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Haferlach, Claudia
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Harder, Lana
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Heidenreich, Olaf
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Nguyen-Khac, Florence
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Machado, Lee
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Minto, Lynne
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Majid, Aneela
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Morrison, Heather
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Schwab, Claire
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Tönnies, Holger
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September 2009
Russell, Lisa J.
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Capasso, Melania
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Vater, Inga
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Bernard, Olivier A.
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Chandrasekaran, Thiruppavaii
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Griffith, Mike
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Irving, Julie
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Kearney, Lyndal
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Moorman, Anthony V.
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Rand, Vikki
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Strefford, Jonathan C.
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Dyer, Martin J. S.
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Siebert, Reiner
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Harrison, Christine J.
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Takashi, Akasaka
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Calasanz, Maria Jose
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Chapiro, Elise
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Gesk, Stephan
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Guttery, David S.
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Haferlach, Claudia
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Harder, Lana
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Heidenreich, Olaf
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Nguyen-Khac, Florence
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Machado, Lee
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Minto, Lynne
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Majid, Aneela
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Morrison, Heather
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Schwab, Claire
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Tönnies, Holger
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