title: LDOC1 mRNA is differentially expressed in chronic lymphocytic leukemia and predicts overall survival in untreated patients.
abstract: 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. 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 (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.
authors.affiliation: Departments of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hatice
authors.initials: H
authors.lastname: Duzkale
authors.forename: Carmen D
authors.initials: CD
authors.lastname: Schweighofer
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Coombes
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Barron
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: John
authors.initials: J
authors.lastname: Pfeifer
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Majewski
authors.forename: Bogdan A
authors.initials: BA
authors.lastname: Czerniak
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Jorgensen
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Emil J
authors.initials: EJ
authors.lastname: Freireich
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D001402:B-Lymphocytes / Q000502:physiology; D002051:Burkitt Lymphoma; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C120625:LDOC1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins