Your browser doesn't support javascript.
loading
Trisomy 12 chronic lymphocytic leukemia expresses a unique set of activated and targetable pathways.
Abruzzo, Lynne V; Herling, Carmen D; Calin, George A; Oakes, Christopher; Barron, Lynn L; Banks, Haley E; Katju, Vikram; Keating, Michael J; Coombes, Kevin R.
Afiliación
  • Abruzzo LV; Department of Pathology, The Ohio State University, Columbus, OH, USA lynne.abruzzo@osumc.edu.
  • Herling CD; Department I for Internal Medicine and Center of Integrated Oncology, University of Cologne, Germany.
  • Calin GA; Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
  • Oakes C; Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
  • Barron LL; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Banks HE; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Katju V; Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
  • Keating MJ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Coombes KR; Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
Haematologica ; 103(12): 2069-2078, 2018 12.
Article en En | MEDLINE | ID: mdl-29976738
ABSTRACT
Although trisomy 12 (+12) chronic lymphocytic leukemia (CLL) comprises about 20% of cases, relatively little is known about its pathophysiology. These cases often demonstrate atypical morphological and immunophenotypic features, high proliferative rates, unmutated immunoglobulin heavy chain variable region genes, and a high frequency of NOTCH1 mutation. Patients with +12 CLL have an intermediate prognosis, and show higher incidences of thrombocytopenia, Richter transformation, and other secondary cancers. Despite these important differences, relatively few transcriptional profiling studies have focused on identifying dysregulated pathways that characterize +12 CLL, and most have used a hierarchical cytogenetic classification in which cases with more than one recurrent abnormality are categorized according to the abnormality with the poorest prognosis. In this study, we sought to identify protein-coding genes whose expression contributes to the unique pathophysiology of +12 CLL. To exclude the likely confounding effects of multiple cytogenetic abnormalities on gene expression, our +12 patient cohort had +12 as the sole abnormality. We profiled samples obtained from 147 treatment-naïve patients. We compared cases with +12 as the only cytogenetic abnormality to cases with only del(13q), del(11q), or diploid cytogenetics using independent discovery (n=97) and validation (n=50) sets. We demonstrate that CLL cases with +12 as the sole abnormality express a unique set of activated pathways compared to other cytogenetic subtypes. Among these pathways, we identify the NFAT signaling pathway and the immune checkpoint molecule, NT5E (CD73), which may represent new therapeutic targets.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trisomía / Cromosomas Humanos Par 12 / Leucemia Linfocítica Crónica de Células B / Regulación Leucémica de la Expresión Génica / Perfilación de la Expresión Génica Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Haematologica Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trisomía / Cromosomas Humanos Par 12 / Leucemia Linfocítica Crónica de Células B / Regulación Leucémica de la Expresión Génica / Perfilación de la Expresión Génica Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Haematologica Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos