LDOC1 mRNA is differentially expressed in chronic lymphocytic leukemia and predicts over-all survival in untreated patients

[Guest guest]

BlankLDOC1 mRNA is differentially expressed in chronic lymphocytic leukemia and

predicts over-all survival in untreated patients.

H Duzkale, CD Schweighofer, KR Coombes, LL Barron, A Ferrajoli, S O'Brien, WG

Wierda, J Pfeifer, T Majewski, BA Czerniak, JL nsen, LJ Medeiros, EJ

Freireich, MJ Keating, and LV Abruzzo

Blood, February 10, 2011;

Department of Hematopathology, The University of Texas M.D. Cancer

Center, Houston, TX, United States;

We previously identified LDOC1 as one of the most significantly differentially

expressed genes in untreated 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. In this study, we have

investigated LDOC1 mRNA expression in a large cohort of untreated CLL patients,

as well as in normal peripheral blood B-cell subsets and primary small B-cell

lymphoma samples. We have confirmed that LDOC1 is dramatically down-regulated in

mutated CLL cases compared to unmutated cases, and have identified a new splice

variant, LDOC1S. We show that LDOC1 is expressed in NBC subsets (na?ve >

memory), suggesting that it may play a role in normal B cell development. It is

also expressed in primary small B-cell lymphoma samples, in which its expression

is also 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.

PMID: 21310924