TY - JOUR
T1 - LDOC1 mRNA is differentially expressed in chronic lymphocytic leukemia and predicts overall survival in untreated patients
AU - Duzkale, Hatice
AU - Schweighofer, Carmen D.
AU - Coombes, Kevin R.
AU - Barron, Lynn L.
AU - Ferrajoli, Alessandra
AU - O'Brien, Susan
AU - Wierda, William G.
AU - Pfeifer, John
AU - Majewski, Tadeusz
AU - Czerniak, Bogdan A.
AU - Jorgensen, Jeffrey L.
AU - Medeiros, L. Jeffrey
AU - Freireich, Emil J.
AU - Keating, Michael J.
AU - Abruzzo, Lynne V.
PY - 2011/4/14
Y1 - 2011/4/14
N2 - We previously identified LDOC1 as one of the most significantly differentially expressed genes in untreated chronic lymphocytic leukemia (CLL) patients with respect to the somatic mutation status of the immunoglobulin heavy-chain variable region genes. However, little is known about the normal function of LDOC1, its contribution to the pathophysiology of CLL,or its prognostic significance. Inthis study, we have investigated LDOC1 mRNA expression in a large cohort of untreated CLL patients, as well as in normal peripheral blood B-cell (NBC) subsets and primary B-cell lymphoma samples. We have confirmed that LDOC1 is dramatically down-regulated in mutated CLL cases compared with unmutated cases, and have identified a new splice variant, LDOC1S. We show that LDOC1 is expressed in NBC subsets (naive > memory), suggesting that it may play a role in normal B-cell development. It is also expressed in primary B-cell lymphoma samples, in which its expression is associated with somatic mutation status. In CLL, we show that high levels of LDOC1 correlate with biomarkers of poor prognosis, including cytogenetic markers, unmutated somatic mutation status, and ZAP70 expression. Finally, we demonstrate that LDOC1 mRNA expression is an excellent predictor of overall survival in untreated CLL patients.
AB - We previously identified LDOC1 as one of the most significantly differentially expressed genes in untreated chronic lymphocytic leukemia (CLL) patients with respect to the somatic mutation status of the immunoglobulin heavy-chain variable region genes. However, little is known about the normal function of LDOC1, its contribution to the pathophysiology of CLL,or its prognostic significance. Inthis study, we have investigated LDOC1 mRNA expression in a large cohort of untreated CLL patients, as well as in normal peripheral blood B-cell (NBC) subsets and primary B-cell lymphoma samples. We have confirmed that LDOC1 is dramatically down-regulated in mutated CLL cases compared with unmutated cases, and have identified a new splice variant, LDOC1S. We show that LDOC1 is expressed in NBC subsets (naive > memory), suggesting that it may play a role in normal B-cell development. It is also expressed in primary B-cell lymphoma samples, in which its expression is associated with somatic mutation status. In CLL, we show that high levels of LDOC1 correlate with biomarkers of poor prognosis, including cytogenetic markers, unmutated somatic mutation status, and ZAP70 expression. Finally, we demonstrate that LDOC1 mRNA expression is an excellent predictor of overall survival in untreated CLL patients.
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U2 - 10.1182/blood-2010-09-304881
DO - 10.1182/blood-2010-09-304881
M3 - Article
C2 - 21310924
AN - SCOPUS:79954575984
SN - 0006-4971
VL - 117
SP - 4076
EP - 4084
JO - Blood
JF - Blood
IS - 15
ER -