title: 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.
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Russell
authors.forename: Melania
authors.initials: M
authors.lastname: Capasso
authors.forename: Inga
authors.initials: I
authors.lastname: Vater
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Olivier A
authors.initials: OA
authors.lastname: Bernard
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Thiruppavaii
authors.initials: T
authors.lastname: Chandrasekaran
authors.forename: Elise
authors.initials: E
authors.lastname: Chapiro
authors.forename: Stephan
authors.initials: S
authors.lastname: Gesk
authors.forename: Mike
authors.initials: M
authors.lastname: Griffiths
authors.forename: David S
authors.initials: DS
authors.lastname: Guttery
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Olaf
authors.initials: O
authors.lastname: Heidenreich
authors.forename: Julie
authors.initials: J
authors.lastname: Irving
authors.forename: Lyndal
authors.initials: L
authors.lastname: Kearney
authors.forename: Florence
authors.initials: F
authors.lastname: Nguyen-Khac
authors.forename: Lee
authors.initials: L
authors.lastname: Machado
authors.forename: Lynne
authors.initials: L
authors.lastname: Minto
authors.forename: Aneela
authors.initials: A
authors.lastname: Majid
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
authors.forename: Heather
authors.initials: H
authors.lastname: Morrison
authors.forename: Vikki
authors.initials: V
authors.lastname: Rand
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Strefford
authors.forename: Claire
authors.initials: C
authors.lastname: Schwab
authors.forename: Holger
authors.initials: H
authors.lastname: Tönnies
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D004622:Embryo, Mammalian; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D018121:Receptors, Cytokine / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C498762:CRLF2 protein, human; D018121:Receptors, Cytokine