title: LncRNA Expression Discriminates Karyotype and Predicts Survival in B-Lymphoblastic Leukemia.
abstract: Long noncoding RNAs (lncRNA) have been found to play a role in gene regulation with dysregulated expression in various cancers. The precise role that lncRNA expression plays in the pathogenesis of B-acute lymphoblastic leukemia (B-ALL) is unknown. Therefore, unbiased microarray profiling was performed on human B-ALL specimens, and it was determined that lncRNA expression correlates with cytogenetic abnormalities, which was confirmed by qRT-PCR in a large set of B-ALL cases. Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL, and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development.
  
  
  CONCLUSIONS
  lncRNA expression has the potential to segregate the common subtypes of B-ALL, predict the cytogenetic subtype, and indicate prognosis.
authors: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California.
authors: Thilini R
authors: TR
authors: Fernando
authors: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California. Cellular and Molecular Pathology Ph.D. Program, University of California, Los Angeles, Los Angeles, California.
authors: Norma I
authors: NI
authors: Rodriguez-Malave
authors: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California.
authors: Ella V
authors: EV
authors: Waters
authors: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California.
authors: Weihong
authors: W
authors: Yan
authors: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California.
authors: David
authors: D
authors: Casero
authors: Women and Child Health Department-Hematology-Oncology Laboratory, University of Padova, Padova, Italy.
authors: Giuseppe
authors: G
authors: Basso
authors: Women and Child Health Department-Hematology-Oncology Laboratory, University of Padova, Padova, Italy.
authors: Martina
authors: M
authors: Pigazzi
authors: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California. Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, California. drao@mednet.ucla.edu.
authors: Dinesh S
authors: DS
authors: Rao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D015331:Cohort Studies; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D059785:Karyotype; D051379:Mice; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D062085:RNA, Long Noncoding