TY - JOUR
T1 - Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia
AU - Russell, Lisa
AU - Capasso, Melania
AU - Vater, Inga
AU - Akasaka, Takashui
AU - Bernard, Olivier
AU - Calasanz, Maria Jose
AU - Chandrasekaran, Thiruppavaii
AU - Chapiro, Elise
AU - Gesk, Stephen
AU - Griffiths, Mike
AU - Guttery, David
AU - Haferlach, Claudia
AU - Harder, Lana
AU - Heidenreich, Olaf
AU - Irving, Julie
AU - Kearney, Lyndal
AU - Nguyen-Khac, Florence
AU - Machado, Lee
AU - Minto, Lynne
AU - Majid, Aneela
AU - Moorman, Anthony
AU - Morrison, Heather
AU - Rand, Vikki
AU - Strefford, Jonathan
AU - Schwab, Claire
AU - Tonnies, Holger
AU - Dyer, Martin
AU - Siebert, Reiner
AU - Harrison, Christine
PY - 2009/7/29
Y1 - 2009/7/29
N2 - 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
AB - 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
U2 - 10.1182/blood-2009-03-208397
DO - 10.1182/blood-2009-03-208397
M3 - Article
SN - 0006-4971
VL - 114
SP - 2688
EP - 2698
JO - Blood
JF - Blood
IS - 13
ER -