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.
Russell
Lisa J
LJ
Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom.
Capasso
Melania
M
Vater
Inga
I
Akasaka
Takashi
T
Bernard
Olivier A
OA
Calasanz
Maria Jose
MJ
Chandrasekaran
Thiruppavaii
T
Chapiro
Elise
E
Gesk
Stephan
S
Griffiths
Mike
M
Guttery
David S
DS
Haferlach
Claudia
C
Harder
Lana
L
Heidenreich
Olaf
O
Irving
Julie
J
Kearney
Lyndal
L
Nguyen-Khac
Florence
F
Machado
Lee
L
Minto
Lynne
L
Majid
Aneela
A
Moorman
Anthony V
AV
Morrison
Heather
H
Rand
Vikki
V
Strefford
Jonathan C
JC
Schwab
Claire
C
Tönnies
Holger
H
Dyer
Martin J S
MJ
Siebert
Reiner
R
Harrison
Christine J
CJ
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
C498762:CRLF2 protein, human; D018121:Receptors, Cytokine