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

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.

journal_name

Blood

journal_title

Blood

authors

Russell LJ,Capasso M,Vater I,Akasaka T,Bernard OA,Calasanz MJ,Chandrasekaran T,Chapiro E,Gesk S,Griffiths M,Guttery DS,Haferlach C,Harder L,Heidenreich O,Irving J,Kearney L,Nguyen-Khac F,Machado L,Minto L,Majid A,

doi

10.1182/blood-2009-03-208397

subject

Has Abstract

pub_date

2009-09-24 00:00:00

pages

2688-98

issue

13

eissn

0006-4971

issn

1528-0020

pii

blood-2009-03-208397

journal_volume

114

pub_type

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