Genomics

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Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in BCP-ALL


ABSTRACT: Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia We report two 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), whilst the patients with the deletion were younger (median age 4 years). The two abnormalities result in deregulated expression of the cytokine receptor, cytokine receptor-like factor 2, CRLF2 (also known as thymic stromal-derived lymphopoietin receptor, TSLPR). Over-expression 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 over-expression in lymphoid transformation. In Down Syndrome (DS) ALL and two 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. Keyword(s): Global copy number analysis using Agilent oligonucleotide arrays

ORGANISM(S): Homo sapiens

PROVIDER: GSE17165 | GEO | 2009/07/18

SECONDARY ACCESSION(S): PRJNA119765

REPOSITORIES: GEO

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