In:
Blood, American Society of Hematology, Vol. 118, No. 24 ( 2011-12-08), p. 6362-6367
Abstract:
Aberrant activation of the Wnt pathway plays a pathogenetic role in various tumors and has been associated with adverse outcome in acute lymphoblastic leukemia (ALL). LEF1, a key mediator of Wnt signaling, has been linked to leukemic transformation, and recurrent mutations of LEF1 have been identified in pediatric T-ALL. Here we evaluated the prognostic significance of LEF1 expression in B-precursor ALL patients. LEF1 expression was determined by quantitative real-time RT-PCR in 282 adult B-precursor ALL patients treated on 06/99 and 07/03 GMALL trials. Patients were grouped into quartiles (Q1-Q4) according to LEF1 expression levels (LEF1 high, Q4; n = 71; LEF1 low, Q1-Q3; n = 211). Patients with high LEF1 expression had a significantly shorter relapse-free survival (RFS) compared with low LEF1 expressers (5-year RFS: LEF1 high, 27%; LEF1 low, 47%; P = .05). Importantly, high LEF1 expression was also associated with inferior RFS in standard-risk patients and was independently predictive for RFS (P = .02) in multivariate analyses for this subgroup. Thus, high LEF1 expression identifies B-precursor ALL patients with inferior RFS, supporting a pathogenetic role of Wnt signaling in ALL. Standard-risk patients with high LEF1 expression might benefit from early treatment modifications and new molecular therapies, including agents targeting the Wnt pathway.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2011-04-350850
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2011
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
